Method of making certain aryl containing amides

ABSTRACT

Methods of preparing bis-aryl amide and urea compounds of the general formula:   &lt;IMAGE&gt;   wherein x is a divalent amide or urea substituent and Y is a nitrogen containing heterocycle, which compounds are inhibitors of platelet activating factor.

This is a divisional of co-pending application Ser. No. 07/519,523,filed on May 4, 1990, now U.S. Pat. No. 5,077,409.

BACKGROUND OF THE INVENTION

Platelet Activating Factor (PAF),1-0-hexadecyl/octadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine, is anether lipid produced by a variety of different cell types. Recentstudies [Snyder, F., Ann. Rep. Med. Chem., 17, 243 (1982); Pinckard, R.N., et. al., J. Adv. Inflammation Res., 4, 147 (1982); O'Flaherty, J.T., et. al., Clin. Rev. Allergy, 1, 353 (1983); Vargaftig, B. B., et.al., J. Trends. Pharmacol. Sci., 4, 341 (1983)] have shown PAF to be animportant mediator of allergic disease. When injected into mammals, PAFinduces hemodynamic and hematological changes including hypotension,platelet aggregation, neutropenia, disseminated intravascularcoagulation, increases in vascular permeability, bronchoconstriction,tissue injury (hypoxia and necrosis) and eventually death (reviewed byCammussi, G. Kidney Int. 29, 469, 1986). In recent years, it has beenpostulated that PAF is the mediator of tissue injury in mammalsundergoing endotoxic shock due to bacterial sepsis (Terashita, Z., Y.Imura, K. Nishikawa and S. Sumida 1985, Eur. J. Pharmacol. 109:257-261;Doebber, T. W., M. S. Wu, J. C. Robbins, B. M. Choy, M. N. Chang and T.Y. Shen 1985, Biochem. Biophys. Res. Comm. 127:799-808; Inarrea, P.,Gomez-Cambronero, J. Pascual, M. del Carmen Ponte, L. Hernando and M.Sanchez-Crespo. 1985, Immunopharmacology, 9:45-52). These studies, inmammals, have shown that PAF is produced in large amounts when the saidmammal has been treated with endotoxin. In addition, mammals undergoingendotoxic shock exhibit all of the clinical symptoms associated with theadministration of PAF. In addition, PAF is implicated in asthma,respiratory distress syndrome, lung edema and other inflammatory andcardiovascular diseases.

The compounds of the present invention have proven to be specificinhibitors of the biological effects of PAF and are consequently usefulfor the treatment of asthma, anaphylactic and septic (endotoxic) shock,psoriasis, bowel necrosis, adult respiratory distress syndrome,transplant rejection, thrombosis, stroke, cardiac anaphylaxis andcancer.

Concurrently, with the realization that PAF is an important mediator ofinflammatory diseases in mammals, a number of structurally differentantagonists of PAF have been developed. References to some of theseantagonists are listed hereinbelow.

Takatani, M., et al., J. Med. Chem., 32(1), 56-64 (1989)

Terashita, Z., et al., J. Pharmacol. Exp. Ther., 242(1), 263-8 (1987)

Wissner, A, et al., J. Med. Chem., 29(3), 328-33 (1986)

Tomesch, J., U.S. Pat. No. 4,820,718, Apr. 11, 1989

Guthrie, R. W., et al., J. Med. Chem. 32(8) 1820-35 (1989)

Guthrie, R. W., et al., U.S. Pat. No. 4,786,646, Nov. 22, 1988

BRIEF SUMMARY OF THE INVENTION

The compounds of the present invention are represented by the Formula I:##STR2## wherein: (A) X is a divalent radical selected from the groupconsisting of: ##STR3## wherein p is the integer 0 or 1; n is theinteger 0, 1, or 2; m is the integer 0, 1, 2 or 3; R₃ is selected fromthe group consisting of C₁ -C₄ alkyl, C₁ -C₄ alkoxy, and C₁ -C₄alkylamino; (B) R₁ represents one or more substituents of the aromaticring which may be the same or different and is selected from the groupconsisting of: (i) C₁ -C₂₅ alkyl, C₁ -C₂₅ alkenyl, C₁ -C₂₅ alkoxy, C₁-C₂₅ thioalkyl, C₁ -C₂₅ alkenyloxy, phenyl, phenoxy, substituted phenyland substituted phenoxy wherein the substituents are selected from thegroup consisting of C₁ -C₂₀ alkyl, C₁ -C₂₀ alkoxy, halogen andtrifluoromethyl; (ii) hydrogen, halogen, trifluoromethyl, cyano andnitro; (iii) --CO₂ R₄, --CONHR₃, --CHO, OCONHR₄, and --NHCOR₄ wherein R₄is selected from the group consisting of C₁ -C₂₅ alkyl, C₁ -C₂₅ alkenyl,phenyl and substituted phenyl wherein the substituents are selected fromthe group consisting of C₁ -C₂₀ alkyl, C₁ -C₂₀ alkoxy, halogen andtrifluoromethyl; (C) the moiety R₂ represents one or more substituentsof the aromatic ring which may be in any position and are selected fromthe group consisting of hydrogen C₁ -C₅ alkyl, C₁ -C₅ alkoxy andhalogen; (D) the moiety --(CH₂)_(q) --Y is a moiety wherein q is aninteger from 0 to 1 and Y represents a single substituent of thearomatic ring which may occupy any position and is a stable, optionallysubstituted mono or bicyclic aromatic heterocycle with 5-6 memberedrings containing at least one nitrogen atom and optionally one or moreother nitrogen or sulfur atoms; the substituents of the heterocycle areselected from the group consisting of C₁ -C₆ alkyl, C₁ -C₆ acyl, or C₁-C₆ alkoxy. A preferred embodiment is compounds of Formula I wherein Yis: ##STR4## wherein the moiety R₅ is one or more substituents of theheterocyclic ring which may be the same or different and are selectedfrom the group consisting of hydrogen, C₁ -C₆ alkyl, C₁ -C₆ acyl, or C₁-C₆ alkoxy; R₆ is C₁ -C₄ alkyl; q is 0 or 1; and the pharmacologicallyacceptable salts thereof.

DETAILED DESCRIPTION OF THE INVENTION

The preparation of the compound of the present invention encompassed byFormula 8 is described hereinbelow in Flowsheet A wherein R₁, R₂ and nare described hereinabove. The moiety R₇ is a C₁ to C₆ alkyl group. R₈is selected from the group consisting of --CH₂ OH, and --CO₂ R₇. Y' isan optionally substituted mono or bicyclic heterocycle with 5-6 memberedrings containing at least one nitrogen atom (which is bonded directly tothe methylene group) and optionally one or more nitrogen or sulfuratoms.

In a specific embodiment, Y' is selected from the group consisting of:##STR5## wherein R₅ and R₆ are as described hereinabove.

According to sequence of reactions outlined in flowchart A, thecarboxylic acid ester 2 is hydrolyzed with sodium or potassium hydroxidein aqueous alcohol to give the carboxylic acid 3 which is converted tothe acid chloride 4 using oxalyl chloride in the presence of a catalyticamount of dimethylformamide (DMF) in an inert solvent such as methylenechloride. The acid chloride is reacted with amine 5 in the presence of abase such as triethylamine or pyridine to give the amides represented byFormula 6. For those compounds wherein R₈ is --CH₂ OH (6a), the alcoholis converted to the mesylate using methanesulfonyl chloride and a basesuch as triethylamine in an inert solvent such as tetrahydrofuran (THF).This mesylate can, without isolation, be converted to the bromide 7, bytreating the reaction mixture with an excess of lithium bromide.Alternatively, the bromide can be prepared directly by heating 6a in HBrin acetic acid. Alkylation of bromide 7 with a nitrogen containingheterocycle Y' in an inert solvent with heating gives the compounds ofthis invention represented by Formula 8.

In those cases wherein R₈ is --CO₂ R₇ (6b), the ester group is firstreduced with lithium borohydride in refluxing THF to give the alcohol 6awhich is converted to the compounds of this invention 8 as describedhereinabove. ##STR6##

The preparations of compounds of this invention represented by Formulas13-16 are described hereinbelow in Flowsheet B wherein R₁, R₂, R₆, p andn are described hereinabove. The moiety Y" is an optionally substitutedmono or bicyclic heterocycle with 5-6 membered rings containing at leastone nitrogen atom; the heterocycle is bonded to the molecule throughattachment of one of its carbon atoms. More specifically, Y" is selectedfrom the group consisting of: ##STR7## The moiety Y"' is an optionallysubstituted mono or bicyclic heterocycle with 5-6 membered ringscontaining at least one alkylated nitrogen atom; the heterocycle isbonded to the molecule through attachment of one of its carbon atoms.More specifically, Y"' is selected from the group consisting of those ofthe following formula wherein J is the halogen atoms I, or Br or is atrifluoromethyl sulfonyl group: ##STR8##

According to sequence of reactions outlined in Flowchart B, thecarboxylic acid ester 2 is hydrolyzed with sodium or potassium hydroxidein aqueous alcohol to give carboxylic acid 3 which is converted to theacid chloride 4 using oxalyl chloride in the presence of a catalyticamount of dimethylformamide (DMF) in an inert solvent such as methylenechloride. The acid chloride is reacted with amine 9 in the presence of abase such as triethylamine/pyridine to give the amides represented byFormula 10. The aromatic iodides 10 or the benzyl bromides representedby Formula 7 (see Flowsheet A) are heated with a trimethyl tinsubstituted heterocycle such as 11 or 12 in an inert solvent such as THFin the presence of a catalytic amount of a palladium catalyst to givethe compounds of this invention 13 or 15, respectively. Compounds 13 or15 can be alkylated with an alkyl halide oralkyltrifluoromethanesulfonate to give the charged compounds of thisinvention 14 and 16, respectively.

The trimethyltin substituted heterocycles such as 11 or 12 needed toprepare some of the compounds of this invention can be prepared asdescribed in the following references: Dondoni, P., Mastellari, A. R.,Medici, A.; Negrini, E., Pedrini, P. Synthesis 757 (1986); Bailey, T.R., Tet. Lett. 27, 4407 (1986); Jutzi, P. and Gilge, U., J. Organmet.Chem., 246, 163 (1983). ##STR9##

The preparation of the compounds of this invention encompassed byFormula 20 is described hereinbelow in Flowsheet C wherein R₁, R₂, R₃,Y', R₆, m, n, and p are described hereinabove. The group R₉ is C₁ -C₄alkyl. According to the sequence of reactions outlined in Flowsheet C,the benzyl alcohol 6a (see Flowsheet A) is reduced with a reducing agentsuch as lithium aluminum hydride in an inert solvent such as THF at 0°to 65° to give the amine 17. The reaction of 17 with at least twoequivalents of an anhydride, acid chloride, isocyanate, or chloroformatein the presence of a base such as pyridine in methylene chloride givesthe bis-functionalized derivative 18. When R₃ is C₁ -C₄ alkyl or C₁ -C₄alkoxy, the ester and carbonate groups, respectively, can be selectivelyhydrolyzed. Treating the resulting benzyl alcohol with methanesulfonylchloride and a base such as triethylamine in THF gives a mesylate whichcan, without isolation, be converted to bromide 19 by reacting it with alarge excess of lithium bromide. Alternatively, when R₃ is C₁ -C₄ alkyl,C₁ -C₄ alkoxy, or C₁ -C₄ alkylamino, the bromide 19 can be prepareddirectly by heating 18 in HBr-acetic acid. Alkylation of 19 with anitrogen-containing heterocycle Y' in an inert solvent with heatinggives the compounds of this invention represented by Formula 20.##STR10##

The preparations of compounds of this invention represented by Formulas23, 24, 25 and 26 are described hereinbelow in Flowsheet D wherein J,R₁, R₂, R₃, R₅, R₆, R₉, m, n, p, Y", and Y"' are described hereinabove.According to the sequence of reactions outlined hereinbelow in FlowsheetD, the amides represented by Formula 10 (see Flowsheet B) are reducedwith lithium aluminum hydride or similar reducing agent to give theamines 21. The reaction of these amines with an anhydride, acidchloride, isocyanate, or chloroformate gives aromatic iodides 22. Thearomatic iodides 22 or the benzyl bromides represented by Formula 19(see Flowsheet C) are heated with a trimethyltin substituted heterocyclesuch as 11 or 12 in an inert solvent such as THF in the presence of acatalytic amount of a palladium catalyst to give the compounds of thisinvention 23 or 25, respectively. Compounds 23 or 25 can be alkylatedwith an alkyl halide or alkyltrifluoromethanesulfonate to give thecharged compounds of this invention 24 and 26, respectively. ##STR11##

Compounds of this invention represented by Formula 33 are prepared asoutlined hereinbelow in Flowsheet E wherein R₂, R₅, R₁, n, R₆ and J areas defined hereinabove. The reaction of the aromatic nitro fluorides 27with the imidazoles 28 in the presence of a base such as potassiumcarbonate in dimethylsulfoxide (DMSO) at elevated temperature gives thenitro compounds 29. These are reduced catalytically with hydrogen inbuffered methanol to give the substituted anilines 30. The reaction ofacid chloride 4 (see Flowsheet A) with the anilines 30 gives thecompounds of this invention represented by Formula 31. Alkylation of 31with an alkyl halide or trifluoromethylsulfonate 32 gives the chargedcompounds of this invention represented by Formula 33. ##STR12##

The preparation of compounds of this invention encompassed by Formula 41is described hereinbelow in Flowsheet F wherein R₁, R₂, p, R₇ and Y' areas described hereinabove. According to the sequence of reactionsoutlined in Flowsheet F, alkylation of phenol 34 with an alkylbromoacetate using potassium carbonate in refluxing acetone gives thecarboxylic acid ester 35. The substituted phenols 34 needed to preparethe compounds can be prepared as described in the following lo U.S. Pat.Nos.: 4,697,031; 4,699,990 and 4,640,913 and in our copendingapplication Ser. No. 286,193, filed in December 1988. The carboxylicacid ester 35 is hydrolyzed with sodium or potassium hydroxide inaqueous alcohol to give the carboxylic acid 36 which is converted to theacid chloride 37 using oxalyl chloride in the presence of a catalyticamount of dimethylformamide (DMF) in an inert solvent such as methylenechloride. The acid chloride is reacted with amine 38 in the presence ofa base such as triethylamine or pyridine to give the amides representedby Formula 39. The alcohol 39 is converted to the mesylate usingmethanesulfonyl chloride and a base such as triethylamine in an inertsolvent such as tetrahydrofuran (THF). This mesylate can, withoutisolation, be converted to the bromide 40, by treating the reactionmixture with an excess of lithium bromide. Alternatively, the bromidecan be prepared directly by heating 39 in HBr in acetic acid. Alkylationof bromide 40 with a nitrogen-containing heterocycle Y, in an inertsolvent with heating gives the compounds of this invention representedby Formula 41. ##STR13##

The preparations of compounds of this invention represented by Formulas43-46 are described hereinbelow in Flowsheet G wherein R₁, R₂, R₆, p,R₅, J, Y" and Y"' are as described hereinabove. According to thesequence of reactions outlined in Flowsheet G, the acid chloride 37 isreacted with amine 9 in the presence of a base such as triethylamine inpyridine to give the amides represented by Formula 42. The aromaticiodides 42 or the benzyl bromides represented by Formula 40 (seeFlowsheet F) are heated with a trimethyl tin substituted heterocyclesuch as 11 or 12 in an inert solvent such as THF in the presence of acatalytic amount of a palladium catalyst to give the compounds of thisinvention 43 or 45, respectively. Compounds 43 or 45 can be alkylatedwith an alkyl halide or alkyltrifluoromethanesulfonate to give thecharged compounds of this invention 44 and 46, respectively. ##STR14##

Compounds of this invention represented by Formula 52 are prepared asoutlined hereinbelow in Flowsheet H wherein R₁, R₂, p, and Y' are asdescribed hereinabove. The reaction of carboxylic acid 47 [J. Amer.Chem. Soc., 62 1180 (1940)] with oxalyl chloride in an inert solventsuch as methylene chloride in the presence of a catalytic quantity ofdimethylformamide (DMF) gives the acid chloride 48. Substitutednitrobenzenes 49 can be reduced to the corresponding anilines 50 bycatalytic hydrogenation in an alcohol solvent. The reaction of 50 and 48in tetrahydrofuran in the presence of pyridine gives the amides 51.Alkylation of 51 with a nitrogen-containing heterocycle Y' in an inertsolvent such as acetonitrile at elevated temperature gives the compoundsof this invention represented by Formula 52. ##STR15##

The urea compounds of this invention represented by Formula 56 areprepared as shown hereinbelow in Flowsheet I wherein R₁, R₂, p, and Y'are as described hereinabove. The anilines 50 (see Flowsheet H) areconverted to the isocyanates 53 by treatment with triphosgene,triethylamine, and a small quantity of N,N-dimethylamino pyridine inmethylene chloride. The reaction of 53 with amino alcohol 38 catalyzedby pyridine in THF gives the urea 54. The bromide 55 is prepared byreaction of 54 with hydrobromic acid in acetic acid. Alkylation of 55with a nitrogen-containing heterocycle Y' in an inert solvent such asacetonitrile at elevated temperature gives the urea compounds of thisinvention represented by Formula 56. ##STR16##

The compounds of this invention are tested for pharmacological activityas described in the following tests.

Platelet Activating Factor Antagonism In Vitro

Test compounds are evaluated as PAF receptor antagonists in vitro bymeasuring inhibition of PAF (platelet activating factor) inducedplatelet aggregation. Platelet aggregation is measured by a modificationof the method described in A. Wissner, et. al., J. Med. Chem., 27 1174,1984.

Approximately 120-240 ml of blood is collected by cardiac puncture fromunanesthetized male New Zealand White rabbits (Whaley's Summit ViewFarms, Belvedere, N.J.) with the use of 3.2% sodium citrateanticoagulant (1 part of citrate/10 parts of blood). All syringes andpipets are plastic. The blood is gently mixed and immediatelycentrifuged at 800 rpm for 10-15 minutes at room temperature to recoverthe platelet rich plasma (PRP). Platelet poor plasma (PPP) is preparedby centrifuging PRP at 2800 rpm for 10 minutes at room temperature.

Dilutions (1:3000) of PRP in Isoton® diluent are made and plateletcounts are determined on a Coulter Thrombocounter which is standardizedwith platelet reference standards (Interscience Platelet Control,Portland, Oreg.). PRP platelet counts are adjusted to approximately400,000-500,000 platelets/μl by the addition of PPP.

L-PAF (Platelet Activating Factor) is obtained from Calbiochem. A stocksolution of 1-2 E-3M is prepared in 10% ethanol in water or 100%methanol and serial working dilutions are made using saline. 1-2 E-3Mstock solutions of test compounds are prepared in 100% methanol andserially diluted in PBS. All solutions are made up in plastic tubes,stored on ice and protected from heat and light. Solutions are preparedfresh or frozen at -20° C. and used within 48 hours.

Incubation mixtures consisted of 400 μl PRP, 50 μl of saline diluent ortest compound and 50 μl of PAF agonist. More specifically, 400 μl of PRPis stabilized in a cuvette for 1-2 minutes at 37° C. in the aggregometerto achieve a stable baseline, then 50 μl of saline or test compound isadded and incubated for 5 minutes before addition of the challengeconcentration of PAF. A submaximal concentration is determined from thedose response curve for PAF for that experiment. In general, thechallenge concentration is 5E-8 or IE-7M. Aggregation is monitored for 5minutes. Samples containing test compound or diluent are runsimultaneously for comparison. Test compounds are initially evaluated ata screening concentration of 1E-5M. Those producing ≧50% inhibition ofthe magnitude of aggregation at IE-5M are then reevaluated at severalfinal concentrations ranging from 1E-8M to 5E-5M and IC50 values aredetermined from the dose response curve.

The recording equipment consists of a dual channel Chronologaggregometer connected to a dual channel 10MV full scale deflectionOmniscribe chart recorder (Houston Instruments). The chart recorder iscalibrated daily with the use of a suspension of Bio-Rad latex beads(S-X 12 400 mesh) which has a density slightly greater than rabbit PRP.The bead suspension is used to set the 0% light transmission mark andclear water is used to set the 100% light transmission mark. Theselimits defined a full scale deflection. The aggregation traces areanalyzed by a digitizing method (C. Kohler and B. Zoltan, J. Pharm.Methods, 12, 113, 1984) with x, y coordinate data stored in a computerfile. A suitable program computes parameters of interest such as themagnitude of aggregation.

The results of tests on representative compounds of this inventionappear in Table I.

                                      TABLE I                                     __________________________________________________________________________    In Vitro PAF Antagonism:                                                      Inhibition of PAF Induced Platelet Aggregation                                In Rabbit Platelet Rich Plasma                                                Compound          Dose (M).sup.a                                                                      % INH.sup.b                                                                        IC.sub.50 (M).sup.c                                                                PAF Chall Conc (M)                          __________________________________________________________________________    3-[[3-[[[4-(tetradecyloxy)                                                                      .00001                                                                              98.0 1.200E-07                                                                          5E-9                                        phenyl]acetyl]amino]phenyl]                                                                     .000001                                                                             93.0      5.0000E-08                                  methyl]thiazolium bromide                                                                       .0000025                                                                            97.0      5.0000E-08                                                    .000001                                                                             62.0 6.200E-07                                                                          5.0000E-08                                                    .00001                                                                              100.0                                                                              1.000E-08                                                                          5.0000E-08                                                    .00001                                                                              100.0                                                                              2.800E-07                                                                          5.0000E-08                                  2,3-dimethyl-1-[4-[[[4-(tetra-                                                                  .00001                                                                              62.0 4.510E-06                                                                          5.0000E-08                                  decyloxy)phenyl]acetyl]amino]                                                 phenyl]1H-imidazolium iodide                                                  2,3-dimethyl-1-[3-[[[4-(tetra-                                                                  .00001                                                                              80.0 2.470E-06                                                                          5.0000E-08                                  decyloxy)phenyl]acetyl]amino]                                                 phenyl]1H-imidazolium iodide                                                  N-[3-(2-methyl-1H-imidazol-1-                                                                   .00001                                                                              34.0      5.0000E-08                                  yl)phenyl]-4-(tetradecyloxy)-                                                                   .00001                                                                              39.0 1.860E-05                                                                          5.0000E-08                                  benzeneacetamide monohydrochloride                                            5-methyl-3-[[3-[[[3-(tetra-                                                                     .00001                                                                              100.0                                                                              1.060E-06                                                                          5E-9                                        decyloxy)phenyl]acetyl]amino]                                                                   .00001                                                                              27.0      5.0000E-08                                  phenyl]methyl]thiazolium                                                                        .00001                                                                              100.0                                                                              4.900E-07                                                                          5.0000E-08                                  bromide           .00001                                                                              89.0 1.270E-06                                                                          5.0000E-08                                  5-methyl-3-[[2-[[[3-(tetra-                                                                     .00001                                                                              27.0 3.400E-05                                                                          5E-9                                        decyloxy)phenyl]acetyl]amino]-                                                                  .00001                                                                              23.0      5.0000E-08                                  phenyl]methyl]thiazolium                                                      bromide                                                                       3-[[3-[acetyl[2-[4-(tetra-                                                                      .00001                                                                              85.0 2.910E-06                                                                          8.0000E-09                                  decyloxy)phenyl]ethyl]amino]                                                                    .00001                                                                              69.0 4.300E-06                                                                           .0000005                                   phenyl]methyl]-5-methyl-                                                      thiazolium bromide                                                            3-[[2-[[[4-(hexadecyloxy)                                                                       .00001                                                                              60.0 1.120E-05                                                                          1.0000E-08                                  phenoxy]acetyl]amino]phenyl]                                                                    .00001                                                                              83.0 3.800E-06                                                                           .0000005                                   methyl]-5-methyl-thiazolium                                                   bromide                                                                       3-[[3-[[[4-(hexadecyloxy)                                                                       .00001                                                                              93.0 4.400E-06                                                                          1.0000E-08                                  phenoxy]acetyl]amino]phenyl]                                                                    .00001                                                                              72.0 5.000E-06                                                                          5.0000E-08                                  methyl]-5-methyl-thiazolium                                                   bromide                                                                       5-methyl-3-[[3-[[4-(tetra-                                                                      .00001                                                                              54.0 5.970E-06                                                                          5.0000E-08                                  decyloxy)benzoyl]amino]phenyl]                                                methyl]-thiazolium bromide                                                    3-[[3-[acetyl[[4-(tetradecyl-                                                                   .00001                                                                              98.0 5.400E-07                                                                          5.0000E-08                                  oxy)phenyl]methyl]amino]-                                                                       .00001                                                                              100.0                                                                              5.000E-08                                                                          5.0000E-08                                  phenyl]methyl]-5-methyl-                                                                        .00001                                                                              90.0 2.000E-07                                                                          5.0000E-08                                  thiazolium bromide                                                            5-methyl-3-[[4-[[[4-(tetra-                                                                     .00001                                                                              92.0 1.800E-07                                                                          5.0000E-08                                  decyloxy)phenyl)acetyl]amino]-                                                                  .00001                                                                              100.0                                                                              3.200E-07                                                                          5.0000E-08                                  phenyl]methyl]-thiazolium                                                                       .00001                                                                              92.0 1.300E-06                                                                          5.0000E-08                                  bromide                                                                       5-methyl-3-[[3-[[[4-(tetra-                                                                     .00001                                                                              89.0 2.700E-06                                                                          5.0000E-08                                  decyloxy)phenyl]amino]car-                                                    bonyl]phenyl]methyl]-thiazolium                                               bromide                                                                       5-methyl-3-[[3-[[[[4-(tetra-                                                                    .00001                                                                              92.0 1.500E-06                                                                          5.0000E-08                                  decyloxy)phenyl]amino]carbonyl]                                                                 .00005                                                                              80.0 1.690E-05                                                                           .0000001                                   amino]phenyl]methyl]-thiazolium                                               bromide                                                                       3-methyl-2-[3-[[[4-(tetra-                                                                      .00001                                                                              46.0 1.200E-05                                                                          5.0000E-08                                  decyloxy)phenyl]acetyl]amino]                                                 phenyl]-thiazolium chloride                                                   5-methyl-3-[[3-[[(methylamino)                                                                  .00001                                                                              90.0 4.600E-07                                                                          5.0000E-08                                  carbonyl]-[[4-(tetradecyloxy)                                                                   .00001                                                                              95.0 1.090E-06                                                                           .0000001                                   phenyl]methyl]amino]phenyl]                                                   methyl]-thiazolium bromide                                                    3-[[4-[acetyl[[[4-(tetradecyl-                                                                  .00001                                                                              84.0 2.100E-06                                                                          5.0000E-08                                  oxy)phenyl]methyl]amino]                                                      phenyl]methyl]-5-methyl-                                                      thiazolium bromide                                                            1-[[3-[acetyl[[4-(tetradecyl-                                                                   .00001                                                                              52.0 1.200E-05                                                                          5.0000E-08                                  oxy)phenyl]methyl]amino]                                                      phenyl]methyl]-3,4-dimethyl-                                                  pyridinium bromide                                                            3,5-dimethyl-1-[[3-[[[4-(tetra-                                                                 .00001                                                                              84.0      5.0000E-08                                  decyloxy)phenyl]acetyl]amino]                                                 phenyl]methyl]-pyridinium                                                     bromide                                                                       2-[[3-[[[4-(tetradecyloxy)                                                                      .00001                                                                              91.0 1.500E-06                                                                          5.0000E-08                                  phenyl]acetyl]amino]phenyl]                                                   methyl-imidazo[1,5-a]phenyl                                                   bromide                                                                       __________________________________________________________________________     .sup.a dose of compound that gives the indicated % inhibition.                .sup.b the % inhibition of PAF induced platelet aggregation.                  .sup.c the molar concentration of compound that will inhibit 50% of the       platelet aggretation induced by PAF given at the indicated PAF challenge      concentration.                                                           

A. PAF Induced Lethality in Mice

PAF given I.V. to mice causes an immediate hypotensive shock leading todeath in 1 hour or less. Compounds are given intraperitoneally or P.O.at various times before the PAF challenge. Animals alive after 2 hoursare counted and the activity of test compounds expressed as % survivalcorrected for any control (saline treated) animals which survived thePAF challenge. Results of this assay appear in Table II.

                  TABLE II                                                        ______________________________________                                        Effect of Compound Given I.V. or P.O. in Protecting                           Mice from a Lethal Challenge of PAF.sup.a                                                     Dose (P.O.)                                                                              Dose (I.V.)                                                                             % Sur-                                   Compound        mg/kg      mg/kg     vival                                    ______________________________________                                        Control         --         --        10%                                      (saline only)                                                                 5-methyl-3-[[3-[[[3-                                                                          20         --        59%                                      (tetradecyloxy)phenyl]-                                                                       10         --        --                                       acetyl]amino]phenyl]methyl]-                                                                   5         --        40%                                      thiazolium bromide                                                            3-[[3-[acetyl[[4-(tetra-                                                                      20         --        75%                                      decyloxy)phenyl]methyl]-                                                                      10         --        75%                                      amino]phenyl]methyl]-5-                                                                        5         --        52%                                      methyl-thiazolium bromide                                                     3-[[3-[acetyl[[4-(tetra-                                                                      --         1         83%                                      decyloxy)phenyl]methyl]-                                                                      --         .5        83%                                      amino]phenyl]methyl]-5-                                                                       --         .25       100%                                     methyl-thiazolium bromide                                                     5-methyl-3-[[4-[[[4-                                                                          20         --        32%                                      (tetradecyloxy)phenyl]-                                                                        5         --        32%                                      acetyl]amino]phenyl]methyl]-                                                  thiazolium bromide                                                            3-[[3-[[[4-(tetradecyloxy)-                                                                   40         --        40%                                      phenyl]acetyl]amino]phenyl]-                                                  methyl]thiazolium bromide                                                     ______________________________________                                         .sup.a lethal challenge of PAF is 150 μg/kg IV.                       

B. Endotoxin Induced Shock and Mortality in Mice

Endotoxin administration produces a shock-like state characterized byvascular permeability changes, hypotension, neutropenia,thrombocytopenia, multiple organ damage and death. The major mediatorsreleased after endotoxin injection are TNF (tumor necrosis factor), PAF(platelet activating factor) and LL-1 (interleukin I). PAFadministration mimics the signs and symptoms of endotoxin induced shockand death and endotoxin also induces the release of PAF. Therefore, theeffects of endotoxin should be blocked with a PAF antagonist.

Male Balb/c mice (approximately 20 g) are obtained from Charles RiverLaboratories and used after a one-two week acclimation period. Animalsare given (ip) test compound dissolved in saline or water (sonicated andheated) at different time intervals prior to and after the ip injectionof endotoxin (usually 2 hours before LPS endotoxin, and 3-4 hoursafter). Sigma E. Coli endotoxin, 0111:B4, phenol extraction, catalog#L2630 is used for these studies.

For the acute lethality test, the endotoxin dose is determined fromdose-response titrations and adjusted to a dose that is lethal for80-90% (LD₈₀ -LD₉₀) of the mice within a 24 hour period. This LD valueis approximately 50 mg/kg i.p. The number of survivors in each group(control or treated with test compound) is recorded after 24, 48 or 72hours and the treated groups (receiving test compound and endotoxin) arecompared with the untreated, control group (receiving endotoxin only) orsaline control (receiving saline and endotoxin).

For the chronic endotoxin shock model, a lower dose of endotoxin isadministered (generally 15 to 20 mg/kg i.p). This dose gives an LD₈₀ intwo to four days following LPS administration. Test compounds are given2 hours before LPS and 3-4 hours after on the first day, followed by 3or 4 consecutive days of BID dosing. The number of survivors in eachgroup is recorded each day for a period of 5 to 7 days.

One of the test compounds,5-methyl-3-[[3-[[[3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazoliumbromide, known to be a PAF antagonist from in vitro platelet aggregationstudies, when administered ip prior to a lethal ip injection ofendotoxin (Table 2) did show some activity (Table 3). Several of thetest compounds (PAF antagonists) are efficacious in the chronic, lowerdose LPS model when administered i.p. BID daily for several days. (Table4).

                                      TABLE 3                                     __________________________________________________________________________    Effect of Compounds Given I.P. in High Dose Acute Mouse Endotoxemia                       Days % Survival                                                   Treatment   0      1      2     3     4                                       __________________________________________________________________________    Saline Control                                                                            30/30 (100%)                                                                          6/30 (20%)                                                                          6/30 (20%)                                                                          6/30 (20%)                                                                          6/30 (20%)                              5-methyl-3-[[3-[[[3-(tetra-                                                               30/30 (100%)                                                                         12/30 (40%)                                                                          4/30 (13%)                                                                          3/30 (10%)                                                                          3/30 (10%)                              decyloxy)phenyl]acetyl]                                                       amino]phenyl]methyl]                                                          thiazolium bromide                                                            __________________________________________________________________________     LPS Endotoxin challenge = 50 mg/kg ip                                         Test cpd given 2 hrs. before and 3-4 hrs. after LPS challenge on day 0,       followed by BID dosing fo 3-4 days.                                      

                                      TABLE 4                                     __________________________________________________________________________    Effect of Compounds Given i.p. in Low Dose, Chronic Mouse Endoxemia                  Days No Surv./tot. (% Survival)                                        Treatment                                                                            0         1      2      3     4      5     6      7                    __________________________________________________________________________    None   30/30 (100)                                                                             18/30 (60)                                                                           10/30 (33)                                                                           10/30 (33)                                                                          10/30 (33)                                                                           10/30 (33)                                                                          10/30                                                                                10/30 (33)           Saline 30/30 (100)                                                                             22/30 (73)                                                                           12/30 (40)                                                                            9/30 (30)                                                                           9/30 (30)                                                                            9/30 (30)                                                                           9/30                                                                                 9/30 (30)           See *1 *30/30 (100)                                                                            27/30 (90)                                                                           13/30 (43)                                                                           12/30 (40)                                                                          12/30 (40)                                                                           12/30 (40)                                                                          12/30                                                                                12/30 (40)                  #30/30 (100)                                                                            25/30 (83)                                                                           20/30 (66)                                                                           19/30 (63)                                                                          19/30 (63)                                                                           19/30 (63)                                                                          19/30                                                                                19/30 (63)           None   30/30 (100)                                                                              7/30 (23)                                                                            5/30 (16)                                                                            4/30 (13)                                                                           4/30 (13)                                                                            4/30 (13)                                                                           4/30 (13)                  Saline 30/30 (100)                                                                              8/30 (26)                                                                            5/30 (16)                                                                            5/30 (16)                                                                           5/30 (16)                                                                            5/30 (16)                                                                           5/30 (16)                  See *2 $30/30 (100)                                                                            22/30 (73)                                                                           10/30 (33)                                                                            8/30 (26)                                                                           7/30 (23)                                                                            7/30 (23)                                                                           7/30 (23)                  None   30/30 (100)                                                                             15/30 (50)                                                                            8/30 (26)                                                                             7/30 (23)                                                                          7/30 (23)                                                                            7/30 (23)                                                                           7/30                                                                                 7/30 (23)           Saline 30/30 (100)                                                                             22/30 (73)                                                                           11/30 (36)                                                                           10/30 (33)                                                                          10/30 (33)                                                                           10/30 (33)                                                                          10/30                                                                                10/30 (33)           See *3 #30/30 (100).sup.                                                                        30/30 (100)                                                                         19/30 (63)                                                                           14/30 (46)                                                                          13/30 (43)                                                                           12/30 (43)                                                                          12/30                                                                                12/30 (43)           None   30/30 (100)                                                                             13/30 (43)                                                                            8/30 (26)                                                                            7/30 (23)                                                                           7/30 923)                                                                            7/30 (23)                                                                           7/30 (23)                  Saline 30/30 (100)                                                                             11/30 936)                                                                            7/30 (23)                                                                            4/30 (13)                                                                           4/30 (13)                                                                            4/30 (13)                                                                           4/30 (13)                  See *4 &30/30 (100)                                                                            27/30 (90)                                                                           18/30 (60)                                                                           18/30 (60)                                                                          18/30 (60)                                                                           18/30 (60)                                                                          17/30 (56)                         &&30/30 (100)                                                                            30/30 (100)                                                                         24/30 (80)                                                                           24/30 (80)                                                                          24/30 (80)                                                                           24/30 (80)                                                                          24/30 (80)                  None   30/30 (100)                                                                             19/30 (63)                                                                            5/30 (16)                                                                            3/30 (10)                                                                           3/30 (10)                                                                            3/30 (10)                                                                           3/30                                                                                 3/30 (10)           Saline 30/30 (100)                                                                             20/30 (66)                                                                            4/30 (13)                                                                            4/30 (13)                                                                           4/30 (13)                                                                            4/30 (13)                                                                           4/30                                                                                 4/30 (13)           See *5 @30/30 (100)                                                                            27/30 (90)                                                                            7/30 (23)                                                                            6/30 (20)                                                                           6/30 (20)                                                                            6/30 (20)                                                                           6/30                                                                                 6/30 (20)                  @@30/30 (100)                                                                           24/30 (80)                                                                           14/30 (46)                                                                           14/30 (46)                                                                          14/30 (46)                                                                           14/30 (46)                                                                          14/30                                                                                14/30                __________________________________________________________________________                                                             (46)                  *1 = 3[[3[[[4(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium      bromide                                                                       *Dose 20 mg/kg                                                                # = Dose 10 mg/kg                                                             *2 =                                                                          3[[3[acetyl[[4(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl5-methyl-th    azolium bromide                                                                $ = Dose 10 mg/kg                                                             *3 =                                                                          5methyl-3-[[3[[[3(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazol    um bromide                                                                     *4 =                                                                          5methyl-3-[[4[[[4(tetradecyloxy)phenyl]acetyl]amino]phenyl]methylthiazoli    m bromide                                                                      & = Dose 20 mg/kg                                                             && = Dose 10 mg/kg                                                            *5 =                                                                          5methyl-3-[[3[[(methylamin)carbonyl[[4(tetradecyloxy)phenyl]methyl]amino]    henyl]methyl]thiazolioum bromide                                               @ = Dose 20 mg/kg                                                             @@ = Dose 10 mg/kg                                                       

In addition to the utilities described hereinabove, many of thecompounds of this invention are useful in the preparation of othercompounds of this invention.

The active compounds of the present invention may be orallyadministered, for example, with an inert diluent, or with an assimilableedible carrier, or they may be enclosed in hard or soft shell capsules,or they may be compressed into tablets, or they may be incorporateddirectly with the food of the diet. For oral therapeutic administration,these active compounds may be incorporated with excipients and used inthe form of tablets, capsules, elixirs, suspensions, syrups and thelike. Such compositions and preparations should contain at least 0.1% ofactive compound. The percentage of the compound in these compositionsmay, of course, be varied and may conveniently be between about 2% toabout 60% of the weight of the unit. The amount of active compound insuch therapeutically useful compositions is such that a suitable dosagewill be obtained. Preferred compositions according to this invention areprepared so that an oral dosage unit contains between about 1 and 250 mgof active compound.

The tablets, capsules and the like may also contain a binder such as gumtragacanth, acacia, corn starch or gelatin; excipients such as dicalciumphosphate; a disintegrating agent such as corn starch, potato starch,alginic acid; a lubricant such as magnesium stearate; and a sweeteningagent such as sucrose, lactose or saccharin. When the dosage unit formis a capsule, it may contain, in addition to materials of the abovetype, a liquid carrier such as a fatty oil.

Various other materials may be present as coatings or to modify thephysical form of the dosage unit. For instance, tablets may be coatedwith shellac, sugar or both. A syrup or elixir may contain, in additionto active ingredient, sucrose as a sweetening agent, methyl andpropylparabens as preservatives, a dye and flavoring such as cherry ororange flavor.

These active compounds may also be administered parenterally. Solutionsor suspensions of these active compounds can be prepared in watersuitably mixed with a surfactant such as hydroxypropylcellulose.Dispersions can also be prepared in glycerol, liquid polyethyleneglycols and mixtures thereof in oils. Under ordinary conditions ofstorage and use, these preparations contain a preservative to preventthe growth of microorganisms.

The pharmaceutical forms suitable for injectable use include sterileaqueous solutions or dispersions and sterile powders for theextemporaneous preparation of sterile injectable solutions ordispersions. In all cases, the form must be sterile and must be fluid tothe extent that easy syringability exists. It must be stable under theconditions of manufacture and storage and must be preserved against thecontaminating action of microorganisms such as bacterial and fungi. Thecarrier can be a solvent or dispersion medium containing, for example,water, ethanol, polyol (e.g. glycerol, propylene glycol and liquidpolyethylene glycol), suitable mixtures thereof, and vegetable oils.

The compounds of this invention may also be administered directly to theairways in the form of an aerosol.

The invention will be further described by the following examples.

EXAMPLE 1 Methyl p-(tetradecyloxy)phenyl acetate

A mixture of 102 g of methyl 4-hydroxyphenyl acetate, 170.2 g oftetradecyl bromide and 93.3 g of potassium carbonate in 1,000 ml ofacetone is refluxed for 24 hours. Another 33.9 g of potassium carbonateis added and reflux continued for an additional 24 hours. An additional33.9 g of potassium carbonate is added and reflux continued for another24 hours. The mixture is filtered and the filtrate evaporated to aresidue which is partitioned between ether and dilute sodium hydroxide.The organic layer is dried and evaporated to a residue which iscrystallized from hexane to give 170.1 g of the desired product as awhite solid, m.p. 36°-38° C.

EXAMPLE 2 p-Tetradecyloxyphenylacetic acid

A mixture of 30 g of methyl p-(tetradecyloxy)phenyl acetate, 13.93 g ofpotassium hydroxide, 15 ml of water and 300 ml of ethyl alcohol isrefluxed for 18 hours. The ethyl alcohol is evaporated and the residueis acidified with hydrochloric acid followed by ether extraction. Theorganic layer is dried and evaporated to a residue which is crystallizedfrom carbon tetrachloride:hexane to give 23.7 g of the desired productas a white solid, m.p. 84°-86° C.

EXAMPLE 3 p-Tetradecyloxyphenylacetyl chloride

A mixture of 21.7 g of p-tetradecyloxyphenylacetic acid and 11.85 g ofoxalyl chloride, 45.5 mg of N,N-dimethylformamide and 250 ml ofmethylene chloride is stirred at ambient temperature for 24 hours. Thesolvent is removed by evaporation and the residue is dissolved in etherand filtered through diatomaceous earth. The filtrate is evaporated togive 22.3 g of the desired product as a white solid.

EXAMPLE 4 Ethyl 3-[[[4-(tetradecyloxy)phenyl]acetyl]amino]benzoate

A solution of 10.13 g of ethyl 3-amino-benzoate and 6.82 g oftriethylamine in 100 ml of methylene chloride is added dropwise to asolution of p-tetradecyloxyphenylacetyl chloride in 100 ml of methylenechloride over 15 minutes. The mixture is stirred for an additional 2.5hours then washed with dilute hydrochloric acid. The organic layer isevaporated and the residue dissolved in 1.5 liter of ether then washedwith dilute sodium hydroxide. The organic layer is dried and evaporatedto a residue which is crystallized from carbon tetrachloride:hexane togive 24.4 g of the desired product as a white solid, m.p. 91°-94° C.

EXAMPLE 5 N-[3-Hydroxymethyl)phenyl]-4-(tetradecyloxy)benzeneacetamide

To a suspension of ethyl3-[[[4-(tetradecyloxy)phenyl]acetyl]amino]benzoate in ether is added1.85 g of lithium borohydride and 2.71 g of methyl alcohol. The mixtureis refluxed for 2.5 hours followed by the slow addition of water anddilute hydrochloric acid. The mixture is extracted withether:tetrahydrofuran, dried and evaporated to a residue which iscrystallized from carbon tetrachloride to give 8.4 g of the desiredproduct as a white powder, m.p. 120°-125° C.

EXAMPLE 6 N-[3-(Bromomethyl)phenyl]-4-(tetradecyloxy)benzeneacetamide

To a stirred solution of 4.0 g ofN-[3-hydroxymethyl)phenyl]-4-(tetradecyloxy)-benzeneacetamide in 100 mlof tetrahydrofuran is added 1.19 g of triethylamine followed by 1.34 gof methanesulfonyl chloride. Also added is 7.66 g of lithium bromide andcontinued stirring for 24 hours. The solvent is removed under vacuum andthe residue is partitioned between chloroform and water followed by anadditional wash of the organic layer with saturated sodium bicarbonate.The organic layer is dried and filtered through a pad of silica gel. Thefiltrate is evaporated to a residue which is crystallized fromhexane:carbon tetrachloride to give 4.1 g of the desired product as awhite powder, m.p. 116°-118° C.

EXAMPLE 75-Methyl-3-[[3-[[[4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazoliumbromide

A mixture of 3.6 g ofN-[3-(bromomethyl)phenyl]-4-(tetradecyloxy)benzeneacetamide and 3.46 gof 5-methylthiazole in 25 ml of toluene is refluxed under inert gas for1.5 hours, cooled and poured into 200 ml of ether. The organic layer isdecanted and the solid washed with ether and collected to give 3.8 g ofthe desired product as a white solid, m.p. 173°-175° C.

EXAMPLE 8 N-[4-(Hydroxymethyl)phenyl]-4-tetradecyloxy) benzeneacetamide

A solution of 3.4 g of 4-aminobenzyl alcohol in 100 ml of methyleneChloride containing 6.72 g of pyridine is cooled to 0° C. and a solutionof 7.8 g of p-tetradecyloxyphenylacetyl chloride in 100 ml of methylenechloride added with stirring over 30 minutes. Stirring is continued atambient temperature over 4 hours. The mixture is diluted with 300 ml ofchloroform and water added. The mixture is heated to dissolve the solidsthen the organic layer is washed with dilute hydrochloric acid, driedand filtered through a pad of silica gel. The filtrate is concentratedto about 200 ml on a steam bath and 25 ml of hexanes added. The mixtureis cooled and filtered to give 4.8 g of the desired product as a whitesolid, m.p. 135°-147° C.

EXAMPLE 9 N-[4-(Bromomethyl)phenyl]-4-(tetradecyloxy) benzeneacetamide

To a solution of 4.5 g ofN-[4-(hydroxymethyl)phenyl]-4-tetradecyloxy)benzeneacetamide in 100 mlof tetrahydrofuran is added 1.36 g of methanesulfonyl chloride and 1.2 gof triethylamine followed by stirring for four hours at ambienttemperature. The mixture is poured into water and extracted with ether.The organic layer is washed with saturated sodium bicarbonate, dried andfiltered through a small pad of silica gel. The filtrate is evaporatedand the residue crystallized from carbon tetrachloride:hexane to give3.9 g of off-white solid, m.p. 110°-115° C.

EXAMPLE 105-Methyl-3-[[4-[[[4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazoliumbromide

A mixture of 3.5 g ofN-[4-(bromomethyl)phenyl]-4-(tetradecyloxy)benzeneacetamide and 2.69 gof 5-methylthiazole in 45 ml of toluene is refluxed under argon for 6hours, then allowed to stand at ambient temperature overnight. Themixture is diluted with ether then evaporated to a residue which isdissolved in hot tetrahydrofuran and again diluted with ether. The solidis collected by centrifugation and washed with ether several times thendried under vacuum to give 1.9 g of the product as a white powder, m.p.120°-125° C.

EXAMPLE 11 N-[(2-Hydroxymethyl)phenyl]-4-(tetradecyloxy)benzeneacetamide

To a solution of p-tetradecyloxyphenylacetyl chloride in 110 ml oftetrahydrofuran is added a solution of 3.52 g of O-aminobenzyl alcoholand 9.05 g of pyridine in 100 ml of tetrahydrofuran followed by stirringat ambient temperature overnight. The tetrahydrofuran is evaporated to aresidue which is dissolved in chloroform then washed with dilutehydrochloric acid and saturated sodium bicarbonate. The organic layer isdried and filtered through a pad of magnesium silicate. The filtrate isevaporated to a residue which is crystallized from carbon tetrachlorideto give 10.3 g of the desired product as a white solid, m.p. 112°-115°C.

EXAMPLE 12 N-[2-(Bromomethyl)phenyl]-4-(tetradecyloxy) benzeneacetamide

To a solution of 5 g ofN-[(2-hydroxymethyl)phenyl]-4-(tetradecyloxy)benzeneacetamide in 80 mlof tetrahydrofuran is added 1.68 g of methanesulfonyl chloride and 1.48g of triethylamine followed by stirring for 30 minutes. Added 9.57 g oflithium bromide and continued stirring for 2 hours. The mixture ispoured into water and extracted with warm ethyl acetate. The organiclayer is washed with saturated sodium bicarbonate, dried and evaporatedto a residue which is crystallized from hexanes:carbon tetrachloride togive 3.6 g of the desired product as a white solid, m.p. 100°-103° C.

EXAMPLE 13 5-Methyl-3-[[2-[[[4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

A mixture of 3.0 g ofN-[2-(bromomethyl)phenyl]-4-(tetradecyloxy)benzeneacetamide and 2.88 gof 5-methylthiazole in 25 ml of toluene is heated at reflux under argonfor 2.5 hours. The mixture is poured into 200 ml of ether, cooled, thesolid collected, washed with ether and dried to give 3.2 g of thedesired product as a white powder, m.p. 124°-127° C.

EXAMPLE 14 3-(Tetradecyloxy)benzeneacetic acid, methyl ester

A mixture of 46.5 g of 3-hydroxybenzeneacetic acid methyl ester, 77.6 gn-tetradecyl bromide and 42.54 g of potassium carbonate in 500 ml ofacetone is refluxed for 24 hours. Another 15.5 g of potassium carbonateis added and reflux continued for another 24 hours. An additional 15.5 gof potassium carbonate is added and reflux continued for another 24hours. The mixture is filtered and the filtrate evaporated to a residuewhich is poured into water and extracted with ether. The organic layeris dried and evaporated to a residue which is crystallized from hexaneto give 45 g of the desired product as a white solid, m.p. 31°-33° C.

EXAMPLE 15 m-Tetradecyloxyphenylacetic acid

A mixture of 40.5 g of 3-(tetradecyloxy)benzeneacetic acid, methylester, 18.8 g of potassium hydroxide, 15 ml of water and 300 ml of ethylalcohol is refluxed for 4 hours. The solvent is removed and the residuepartitioned between chloroform and dilute hydrochloric acid. The organiclayer is dried and evaporated to a residue which is crystallized fromcarbon tetrachloride:hexane to give 31.8 g of the desired product as awhite solid.

EXAMPLE 16 3-(Tetradecyloxy)benzeneacetyl chloride

A mixture of 20 g of m-tetradecyloxyphenylacetic acid, 10.93 g of oxalylchloride and 41.95 mg of N,N-dimethylformamide in 250 ml of methylenechloride is stirred at ambient temperature for 5 hours. The solvent isremoved and the concentrate dissolved in 1:1 ether:hexane and filteredthrough diatomaceous earth. The filtrate is evaporated to give 21.3 g ofthe desired product as a light yellow solid.

EXAMPLE 17 N-[3-(Hydroxymethyl)phenyl]-3-(tetradecyloxy)benzeneacetamide

To a solution of 10.5 g of 3-(tetradecyloxy)benzeneacetyl chloride in110 ml of tetrahydrofuran is o added a solution of m-aminobenzyl alcoholin 110 ml of tetrahydrofuran containing 9.05 g of pyridine followed bystirring at ambient temperature for 4 hours and storing in arefrigerator over the weekend. The solvent is evaporated and the residueis poured into water and extracted with tetrahydrofuran:ether. Theorganic layer is washed with dilute hydrochloric acid, dried andfiltered through a pad of magnesium silicate. The filtrate is evaporatedand the residue purified by high pressure liquid chromatography using2:1 hexane:ethyl acetate to give 3.6 g of the desired product as a whitepowder, m.p. 108°-110° C. and 5.8 g of a white powder, m.p. 86°-90° C.found to be3-(tetradecyloxy)-[3-[[[3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]benzeneaceticacid methyl ester.

EXAMPLE 18 N-[3-(Bromomethyl)phenyl]-3-(tetradecyloxy) benzeneacetamide

To a solution of 3.3 g ofN-[3-(hydroxymethyl)phenyl]-3-(tetradecyloxy)benzeneacetamide in 60 mlof tetrahydrofuran is added 1.11 g of methanesulfonyl chloride and978.95 mg of triethylamine followed by stirring at ambient temperaturefor 2 hours. Added 6.32 g of lithium bromide and stirred for anadditional 2.5 hours. The reaction is poured into a mixture of saturatedsodium chloride and saturated sodium bicarbonate then extracted withether. The organic layer is dried and evaporated to give the desiredproduct as a white solid, m.p. 104°-106° C.

EXAMPLE 195-Methyl-3-[[3-[[[3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazoliumbromide

A mixture of 4 g ofN-[3-(bromomethyl)phenyl]-3-(tetradecyloxy)benzeneacetamide and 3.84 gof 5-methylthiazole in 40 ml of toluene is refluxed for 1.5 hours underargon, cooled and the solvent evaporated to a residue. The residue ismixed with ether and the solid collected by centrifugation. The solid iswashed several times with ether then dried by vacuum to give 4.3 g ofthe desired product as an off white powder, m.p. 125°-130° C.

EXAMPLE 20 N-[2-(Hydroxymethyl)phenyl]-3-(tetradecyloxy)benzeneacetamide

To a solution of 3.52 g of O-aminobenzyl alcohol and 9.05 g of pyridinein 110 ml of methylene chloride at 0° C. is added a solution of 10.5 gof m-tetradecyloxyphenylacetyl chloride in 110 ml of methylene chlorideover 30 minutes. Stirring is continued at ambient temperature for 2hours. The mixture is washed several times with dilute hydrochloric acidand dried. The solvent is evaporated and the residue crystallized fromcarbon tetrachloride to give 7.7 g of the desired product as a whitesolid, m.p. 100°-103° C.

EXAMPLE 21 N-[2-(Bromomethyl)phenyl]-3-(tetradecyloxy) benzeneacetamide

To a solution of 4 g ofN-[2-(hydroxymethyl)phenyl]-3-(tetradecyloxy)benzeneacetamide in 75 mlof tetrahydrofuran is added 1.19 g of triethylamine and 1.34 g ofmethanesulfonyl chloride, followed by stirring at room temperature for1.5 hours. Added 7.66 g of lithium bromide with stirring continued foran additional 2.5 hours. The solvent is evaporated and the residuepartitioned between chloroform and saturated sodium bicarbonate. Theorganic layer is dried and evaporated to a residue which is crystallizedfrom hexane to give 2.6 g of the desired product as a white solid, m.p.103°-106° C.

EXAMPLE 225-Methyl-3-[[2-[[[3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazoliumbromide

A mixture of 2.3 g ofN-[2-(bromomethyl)phenyl]-3-(tetradecyloxy)benzeneacetamide and 2.21 gof 5-methylthiazole in 40 ml of toluene is refluxed for 2.5 hours underargon. The solvent is evaporated to a residue which is mixed with etherand the resulting solid collected by centrifugation, washed with etherthen dried to give 2.7 g of the desired product as a white powder, m.p.94°-100° C.

According to the methods outlined hereinabove in Flowsheet A anddescribed in detail in Examples 1-22, the compounds of this inventionlisted hereinbelow in List 1 can be prepared. These methods areapplicable to the preparation of the compounds of this invention by oneskilled in the art.

List 1

3-[[2-[[[-4-(tetradecyloxy) phenyl]acetyl]amino]phenyl]methyl]thiazoliumbromide

3-[[2-[[[-3-(tetradecyloxy) phenyl]acetyl]amino]phenyl]methyl]thiazoliumbromide

3-[[2-[[[-2-(tetradecyloxy) phenyl]acetyl]amino]phenyl]methyl]thiazoliumbromide

3-[[2-[[[3-chloro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[2-[[[3-fluoro-2-(tetradecyloxy)phenyl)acetyl]amino)phenyl]methyl]thiazolium bromide

3-[[2-[[[3-acetyl-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[2-[[[3-acetyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[2-[[[3-t-butyl-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[2-[[[3-t-butyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[2-[[[3-methoxy-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[2-[[[3-methoxy-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[2-[[[2-chloro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[2-[[[4-chloro-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[2-[[[4-t-butyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[2-[[[4-methoxy-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[2-[[[4-methoxy-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[3-[[[-4-(tetradecyloxy) phenyl]acetyl]amino]phenyl]methyl]thiazoliumbromide

3-[[3-[[[-3-(tetradecyloxy) phenyl]acetyl]amino]phenyl]methyl]thiazoliumbromide

3-[[3-[[[3-chloro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[3-[[[3-fluoro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[3-[[[3-fluoro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[3-[[[3-acetyl-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[3-[[[3-acetyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[3-[[[3-t-butyl-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[3-[[[3-t-butyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[3-[[[3-methoxy-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[3-[[[3-methoxy-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[3-[[[2-chloro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[3-[[[4-t-butyl-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[3-[[[4-t-butyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[3-[[[4-methoxy-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[-4-(tetradecyloxy) phenyl]acetyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[[[-4-(hexadecyloxy) phenyl]acetyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[[[-3-(tetradecyloxy) phenyl]acetyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[[[-3-(hexadecyloxy) phenyl]acetyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[[[-2-(tetradecyloxy) phenyl]acetyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[[[-2-(hexadecyloxy) phenyl]acetyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[[[3-chloro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[3-chloro-4-(hexadecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[3-chloro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[3-fluoro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[3-fluoro-4-(hexadecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[3-fluoro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[3-acetyl-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[3-acetyl-4-(hexadecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[3-acetyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[3-acetyl-2-(hexadecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[3-t-butyl-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[3-t-butyl-4-(hexadecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[3-t-butyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[3-methoxy-4-(hexadecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[3-methoxy-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[3-methoxy-2-(hexadecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[2-chloro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[2-chloro-4-(hexadecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[4-chloro-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[4-chloro-3-(hexadecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[4-chloro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[4-t-butyl-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[4-t-butyl-3-(hexadecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[4-t-butyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[4-t-butyl-2-(hexadecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[4-methoxy-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[4-methoxy-3-(hexadecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[3-chloro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[3-chloro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[3-fluoro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[3-fluoro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[3-acetyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[3-t-butyl-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[3-t-butyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[3-methoxy-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[3-methoxy-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[2-chloro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[4-chloro-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[4-t-butyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[4-methoxy-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[4-methoxy-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[-4-(dodecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[-3-(dodecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[-2-(dodecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[3-chloro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[3-chloro-2-(dodecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[3-fluoro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[3-fluoro-4-(dodecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[3-fluoro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[3-fluoro-2-(dodecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[3-acetyl-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[3-acetyl-4-(dodecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[3-acetyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[3-t-butyl-4-(dodecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[3-t-butyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[3-t-butyl-2-(dodecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[3-methoxy-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[3-methoxy-4-(dodecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[3-methoxy-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[3-methoxy-2-(dodecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[2-chloro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[4-chloro-3-(dodecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[4-chloro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[4-chloro-2-(dodecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[4-t-butyl-3-(decyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[4-t-butyl-3-(dodecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[4-t-butyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[4-t-butyl-2-(dodecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[4-methoxy-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[4-methoxy-3-(dodecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[4-methoxy-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[4-methoxy-2-(dodecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[3-chloro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[3-fluoro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[3-acetyl-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[3-acetyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[3-t-butyl-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[3-t-butyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[3-methoxy-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[3-methoxy-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[2-chloro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[4-chloro-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[4-chloro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[4-t-butyl-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[4-t-butyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[4-methoxy-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[4-methoxy-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[[-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[[3-chloro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[[3-chloro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[[3-fluoro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[[3-fluoro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[[3-acetyl-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[[3-acetyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[[3-t-butyl-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[[3-t-butyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[[3-methoxy-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[[3-methoxy-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[[2-chloro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[[4-chloro-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[[4-chloro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[[4-t-butyl-3-(tetradecyloxy)phenyl)acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[[4-methoxy-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[3-chloro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[3-chloro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[3-fluoro-4-(tetradecyloxy) phenylacetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[3-fluoro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[3-acetyl-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[3-acetyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[3-t-butyl-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[3-t-butyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[3-methoxy-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[3-methoxy-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[2-chloro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[4-t-butyl-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-([3-[[[4-t-butyl-2-(tetradecyloxy)phenyl)acetyl]amino]phenyl)methyl]thiazolium bromide

2-Methyl-3-[[3-[[[4-methoxy-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl)methyl]thiazolium bromide

2-Methyl-3-[[3-[[[4-methoxy-2-(tetradecyloxy)phenyl]acetyl]amino]Phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[[-4-(tetradecyloxy)phenyl]acetyl]amino]Phenyl]methyl]thiazolium bromide

2-Methyl-3-([4-([(-3-(tetradecyloxy)phenyl]acetyl]amino]Phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[[-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[[3-chloro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[[3-chloro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[[3-fluoro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[[3-fluoro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[[3-acetyl-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[[3-acetyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[[3-methoxy-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[[3-methoxy-2-(decyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[[2-chloro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[[4-chloro-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[[4-chloro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[[4-t-butyl-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[[4-t-butyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[[4-methoxy-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[[4-methoxy-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[3-chloro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[3-chloro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[3-fluoro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[3-fluoro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[3-acetyl-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[3-acetyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[3-t-butyl-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[3-t-butyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[3-methoxy-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[3-methoxy-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[2-chloro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[4-chloro-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[4-chloro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[4-t-butyl-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[4-t-butyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[4-methoxy-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[4-methoxy-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[3-chloro-4-(octyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[3-chloro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[3-fluoro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[3-fluoro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[3-acetyl-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[3-acetyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl -3-[[3-[[[3-t-butyl-4-(decyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[3-t-butyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[3-methoxy-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[2-chloro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[4-chloro-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[4-chloro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[4-t-butyl-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[4-t-butyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[4-methoxy-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[3-chloro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[3-chloro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[3-fluoro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[3-acetyl-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[3-acetyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[3-t-butyl-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[3-t-butyl-2-(tetradecyloxyphenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[3-methoxy-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[3-methoxy-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[2-chloro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[4-chloro-3-(dodecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[4-chloro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[4-t-butyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[4-methoxy-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[4-methoxy-2-(hexadecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazolium bromide

EXAMPLE 23 Methyl p-(tetradecyloxy)benzoate

A well stirred mixture of 100 g of methyl 4-hydroxybenzoate, 182.25 g oftetradecylbromide, 136.26 g of potassium carbonate and 4.93 g of sodiumiodide in 1-liter of acetone is refluxed for 48 hours. The mixture ispoured into ice water, the solid collected and washed with water. Thesolid is dissolved in chloroform and washed with 1N sodium hydroxide,dried and evaporated to a residue which is crystallized from hexanes togive 18.5 g of the desired product as a white solid, m.p. 64°-66° C.

EXAMPLE 24 p-(Tetradecyloxy)benzoic acid

A mixture of 120 g of methyl p-(tetradecyloxy)benzoate, 57.96 g ofpotassium hydroxide, 1-liter of methyl alcohol, 400 ml of ethyl alcoholand 60 ml of water is refluxed for 4.5 hours. A solid is formed and thereaction mixture partitioned between dilute hydrochloric acid andchloroform with some warming. The organic layer is washed with warmdilute hydrochloric acid and dried. The filtrate is evaporated to avolume of 600 ml and an equal volume of hexanes added to form a solidwhich is dried to give 104 g of the desired product as a white solid,m.p. 94°-96° C.

EXAMPLE 25 p-Tetradecyloxybenzoyl chloride

A mixture of 50 g of p-(tetradecyloxy)benzoic acid and 28.46 g of oxalylchloride in 500 ml of chloroform containing 10 drops ofN,N-dimethylformamide is stirred for 18 hours at ambient temperature.The solvent is evaporated and the residue dissolved in ether, filteredand evaporated to give 54 g of the desired product as a white solid.

EXAMPLE 26 N-[3-(Hydroxymethyl)phenyl]-4-(tetradecyloxy)benzamide

To a solution of 8.17 g of m-aminobenzyl alcohol and 16.14 g of pyridinein 200 ml of methylene chloride is added at 0° C. over 30 minutes asolution of 18 g of p-tetradecyloxybenzoyl chloride in 200 ml ofmethylene chloride. Stirring is continued for another 6 hours. Anadditional 400 ml of chloroform and water is added followed by warmingto dissolve all the solids. The warm organic layer is separated andwashed with dilute hydrochloric acid and saturated sodium bicarbonate.The warm organic layer is dried and filtered. The filtrate is dilutedwith an equal volume of hexane and cooled in a refrigerator overnight.The resulting solid is collected and air dried to give 18.4 g of thedesired product as a white solid, m.p. 112°-115° C.

EXAMPLE 27 N-[3-(Bromomethyl)phenyl]-4-(tetradecyloxy)benzamide

To a solution of N-[3-(hydroxymethyl)phenyl]-4-(tetradecyloxy)benzamideand 3.47 g of methanesulfonyl chloride in 200 ml of tetrahydrofuran isadded 3.07 g of triethylamine followed by stirring at ambienttemperature for 2 hours. Also added is 21.93 g of lithium bromidefollowed by stirring at ambient temperature for an additional 3 hours.The mixture is poured into water and extracted with ether. The organiclayer is washed with a mixture of brine and saturated sodium bicarbonatethen dried. The solvent is removed under vacuum and the residuecrystallized from carbon tetrachloride:hexanes to give the desiredproduct as a white solid, m.p. 116°-118° C.

EXAMPLE 285-Methyl-3-[[3-[[[4-(tetradecyloxy)benzoyl]amino]-phenyl]methyl]thiazoliumbromide

A mixture of 4 g of N-[3-(bromomethyl)phenyl]-4-(tetradecyloxy)benzamideand 3.95 g of 5-methylthiazole in 50 ml of toluene is refluxed underargon for 4 hours. The solvent is removed and ether added to theresidue. The solid is collected by centrifugation and washed severaltimes with ether then vacuum dried to give 4.4 g of the desired productas a white powder, m.p. 188°-192° C.

According to the methods outlined hereinabove in Flowsheet A anddescribed in detail in Examples 9-28, the compounds of this inventionlisted herein-below in List 2 can be prepared. These methods areapplicable to the preparation of the compounds of this invention by oneskilled in the art.

List 2

3-[[2-[[-4-(tetradecyloxy) benzoyl]amino)Phenyl]methyl]thiazoliumbromide

3-[[2-[[-3-(tetradecyloxy) benzoyl]amino]Phenyl]methyl]thiazoliumbromide

3-[[2-[[-2-(tetradecyloxy) benzoyl]amino]phenyl]methyl)thiazoliumbromide

3-[[2-[[3-chloro-4-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

3-[[2-[[3-fluoro-2-(tetradecyloxy)benzoyl]amino)phenyl]methyl)thiazolium bromide

3-[[2-[[3-t-butyl-2-(tetradecyloxy)benzoyl]amino]Phenyl]methyl]thiazolium bromide

3-[[2-[[3-methoxy-4-(tetradecyloxy)benzoyl]amino]Phenyl]methyl]thiazolium bromide

3-[[2-[[3-methoxy-2-(tetradecyloxy)benzoyl)amino)Phenyl]methyl]thiazolium bromide

3-[[2-[[2-chloro-4-(tetradecyloxy)benzoyl)amino]Phenyl]methyl)thiazolium bromide

3-[[2-[[4-chloro-3-(tetradecyloxy)benzoyl]amino]Phenyl]methyl]thiazolium bromide

3-[[2-[[4-t-butyl-2-(tetradecyloxy)benzoyl]amino]Phenyl]methyl]thiazolium bromide

3-[[2-[[4-methoxy-3-(tetradecyloxy)benzoyl]amino]Phenyl]methyl)thiazolium bromide

3-[[2-[[4-methoxy-2-(tetradecyloxy)benzoyl]amino)Phenyl]methyl]thiazolium bromide

3-[[3-[[-4-(tetradecyloxy) benzoyl]amino]Phenyl]methyl]thiazoliumbromide

3-[[3-[[-3-(tetradecyloxy) benzoyl]amino]Phenyl]methyl]thiazoliumbromide

3-[[3-[[3-chloro-2-(tetradecyloxy)benzoyl)amino)Phenyl)methyl)thiazolium bromide

3-[[3-[[3-fluoro-4-(tetradecyloxy)benzoyl]amino]Phenyl]methyl]thiazolium bromide

3-[[3-[[3-fluoro-2-(tetradecyloxy)benzoyl]amino]Phenyl]methyl]thiazolium bromide

3-[[3-[[3-methoxy-4-(tetradecyloxy)benzoyl]amino]Phenyl]methyl]thiazolium bromide

3-[[3-[[3-methoxy-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

3-[[3-[[2-chloro-4-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

3-[[3-[[4-t-butyl-3-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

3-[[3-[[4-t-butyl-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

3-[[3-[[4-methoxy-3-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[-4-(tetradecyloxy) benzoyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[[-4-(hexadecyloxy) benzoyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[-3-(tetradecyloxy) benzoyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[[-3-(hexadecyloxy) benzoyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[-2-(tetradecyloxy) benzoyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[[-2-(hexadecyloxy) benzoyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[3-chloro-4-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[3-chloro-4-(hexadecyloxy) benzoyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[[3-chloro-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[3-acetyl-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[3-acetyl-2-(hexadecyloxy) benzoyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[[3-t-butyl-4-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[3-t-butyl-4-(hexadecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[3-t-butyl-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[3-methoxy-4-(hexadecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[3-methoxy-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[3-methoxy-2-(hexadecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[2-chloro-4-(tetradecyloxy)benzoyl]amino]Phenyl]methyl]thiazolium bromide

3-[[4-[[2-chloro-4-(hexadecyloxy) benzoyl]amino]Phenyl]methyl]thiazoliumbromide

3-[[4-[[4-chloro-3-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[4-chloro-3-(hexadecyloxy) benzoyl)amino)Phenyl]methyl]thiazoliumbromide

3-[[4-[[4-chloro-2-(tetradecyloxy)benzoyl]amino]Phenyl]methyl]thiazolium bromide

3-[[4-[[4-t-butyl-3-(tetradecyloxy)benzoyl]amino]Phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[-4-(tetradecyloxy)benzoyl)amino]Phenyl]methyl]thiazolium bromide

5-Methyl-3-((2-((-3-(tetradecyloxy)benzoyl]amino)Phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[-2-(tetradecyloxy)benzoyl]amino]Phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[3-chloro-4-(tetradecyloxy)benzoyl)amino]Phenyl)methyl]thiazolium bromide

5-Methyl-3-[[2-[[3-chloro-2-(tetradecyloxy)benzoyl]amino]Phenyl]methyl)thiazolium bromide

5-Methyl-3-[[2-[[3-fluoro-4-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[3-fluoro-2-(tetradecyloxy)benzoyl]amino]Phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[3-acetyl-2-(tetradecyloxy)benzoyl]amino]Phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[3-t-butyl-4-(tetradecyloxy)benzoyl]amino]Phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[3-t-butyl-2-(tetradecyloxy)benzoyl]amino)phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[3-methoxy-4-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[3-methoxy-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[2-chloro-4-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[4-chloro-3-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[4-t-butyl-2-(tetradecyloxy)benzoyl)amino)Phenyl)methyl)thiazolium bromide

5-Methyl-3-[[2-[[4-methoxy-3-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[-3-(dodecyloxy) benzoyl]amino]phenyl]methyl]thiazoliumbromide

5-Methyl-3-[[3-[[-4-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[-2-(dodecyloxy) benzoyl]amino]phenyl]methyl]thiazoliumbromide

5-Methyl-3-[[3-[[3-chloro-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[3-chloro-2-(dodecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[3-fluoro-4-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[3-fluoro-4-(dodecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[3-fluoro-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[3-fluoro-2-(dodecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[3-acetyl-4-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[3-acetyl-4-(dodecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[3-acetyl-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[3-t-butyl-4-(dodecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[2-chloro-4-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[4-chloro-3-(dodecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[4-chloro-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[4-chloro-2-(dodecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[4-t-butyl-3-(decyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[4-t-butyl-3-(dodecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[4-t-butyl-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[4-t-butyl-2-(dodecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[4-methoxy-3-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[4-methoxy-3-(dodecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[4-methoxy-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[4-methoxy-2-(dodecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[-4-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[-3-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[3-acetyl-4-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[3-acetyl-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[3-t-butyl-4-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[3-t-butyl-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[3-methoxy-4-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[3-methoxy-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[2-chloro-4-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[4-chloro-3-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[4-chloro-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[4-t-butyl-3-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[4-t-butyl-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[4-methoxy-3-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[(4-[[4-methoxy-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[-4-(tetradecyloxy)benzoyl)amino]Phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[3-chloro-4-(tetradecyloxy)benzoyl]amino]Phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[3-t-butyl-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[3-methoxy-4-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[3-methoxy-2-(tetradecyloxy)benzoyl]amino]Phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[2-chloro-4-(tetradecyloxy)benzoyl]amino]Phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[4-chloro-3-(tetradecyloxy)benzoyl]amino]Phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[4-chloro-2-(tetradecyloxy)benzoyl]amino]Phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[4-t-butyl-3-(tetradecyloxy)benzoyl]amino]Phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[4-methoxy-2-(tetradecyloxy)benzoyl]amino]Phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[-4-(tetradecyloxy)benzoyl]amino]Phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[-3-(tetradecyloxy)benzoyl]amino]Phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-((3-([3-chloro-4-(tetradecyloxy)benzoyl]amino)Phenyl)methyl)thiazolium bromide

2-Methyl-3-[[3-[(3-chloro-2-(tetradecyloxy)benzoyl]amino)phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[3-fluoro-4-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[3-fluoro-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[2-chloro-4-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[4-t-butyl-3-(tetradecyloxy)benzoyl]amino]Phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[4-t-butyl-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[4-methoxy-3-(tetradecyloxy) 1benzoyl]amino]Phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[4-methoxy-2-(tetradecyloxy)benzoyl]amino)Phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[-4-(tetradecyloxy)benzoyl]amino]Phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[-3-(tetradecyloxy)benzoyl]amino]Phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[-2-(tetradecyloxy)benzoyl]amino]Phenyl]methyl)thiazolium bromide

2-Methyl-3-[[4-[[3-chloro-4-(tetradecyloxy)benzoyl]amino)phenyl]methyl)thiazolium bromide

2-Methyl-3-[[4-[[3-chloro-2-(tetradecyloxy)benzoyl]amino]Phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[3-fluoro-4-(tetradecyloxy)benzoyl)amino)Phenyl)methyl]thiazolium bromide

2-Methyl-3-[[4-[[3-fluoro-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[3-acetyl-4-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[3-acetyl-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[3-methoxy-4-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[4-methoxy-3-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[4-methoxy-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[-4-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[-3-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[3-chloro-4-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[3-chloro-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[3-fluoro-4-(tetradecyloxy)benzoyl]amino]Phenyl]methyl]thiazolium bromidebenzoyl]amino[2-[[3-fluoro-2-(tetradecyloxy) o]Phenyl]methyl]thiazoliumbromide

4-Methyl-3-[[2-[[3-acetyl-4-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[3-acetyl-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[3-t-butyl-4-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[3-t-butyl-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[3-methoxy-4-(tetradecyloxybenzoyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[3-methoxy-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[4-methoxy-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[-4-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[-3-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[3-chloro-4-(octyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[3-chloro-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[3-fluoro-4-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[3-fluoro-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[3-acetyl-4-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[3-acetyl-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[3-t-butyl-4-(decyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[3-t-butyl-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[3-methoxy-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[2-chloro-4-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[4-chloro-3-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[4-chloro-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[3-chloro-4-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[3-chloro-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[3-fluoro-4-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[3-acetyl-4-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[3-acetyl-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[3-t-butyl-4-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[3-t-butyl-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[3-methoxy-4-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[3-methoxy-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[2-chloro-4-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[4-chloro-3-(dodecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[4-chloro-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[4-t-butyl-2-(tetradecyloxy)benzoyl]amino]phenyl]methyl]thiazolium bromide

EXAMPLE 29 3-[[[4-(Tetradecyloxy)phenyl]methyl]aminobenzenemethanol

To a solution of theN-[3-(hydroxymethyl)phenyl]-4-(tetradecyloxy)benzamide in 80 ml oftetrahydrofuran at 0° C. under argon is added 36.39 ml of 1M lithiumaluminum hydride. Stirred at room temperature for 1 hour and refluxedfor 7 hours. After stirring overnight and cooling to 0° C., ethylacetate is added followed by sodium hydroxide solution until a solidforms. The mixture is diluted with ether, filtered and evaporated to aresidue which is crystallized from hexane to give 6.7 g of the desiredproduct as a white solid, m.p. 72°-75° C.

EXAMPLE 30N-[3-(Hydroxymethyl)phenyl]-N-[[4-(tetradecyloxy)phenyl]methyl]acetamide

To a solution of3-[[[4-(tetradecyloxy)phenyl]methyl]aminobenzenemethanol and 4.76 g ofpyridine in 50 ml of methylene chloride, cooled to 0° C. over thirtyminutes is added a solution of 4.13 g of acetyl chloride in 10 ml ofmethylene chloride. The mixture is stirred at ambient temperature for1.5 hours, diluted with chloroform and washed with dilute hydrochloricacid then saturated sodium bicarbonate. The organic layer is dried andevaporated to a residue which is stirred with 60 ml of ethyl alcohol:1ml of water and 0.84 g of sodium hydroxide for 35 minutes. The mixtureis poured into water and extracted with ether. The organic layer isdried and evaporated to a residue which is crystallized from hexane togive 6.7 g of the desired product as a white solid, m.p. 65°-67° C.

EXAMPLE 31N-[3-(Bromomethyl)phenyl]-N-[[4-(tetradecyloxy)phenyl]methyl]acetamide

To a solution of 6 g ofN-[3-(hydroxymethyl)phenyl]-N-[[4-(tetradecyloxy)phenyl]methyl]acetamidein 100 ml of tetrahydrofuran is added 1.56 g of triethylamine and 1.76 gof methanesulfonyl chloride followed by stirring at ambient temperaturefor 1 hour. Added 11.14 g of lithium bromide and continued stirring foran additional hour. The mixture is poured into water and extracted withether. The organic layer is washed with a solution of saturated sodiumbicarbonate and brine then dried and evaporated to a residue which iscrystallized from petroleum ether to give 6.6 g of the desired productas a white solid, m.p. 56°-58° C.

EXAMPLE 323-[[3-[Acetyl[[4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methylthiazoliumbromide

A mixture of 3 g ofN-[3-(bromomethyl)phenyl]-N-[[4-(tetradecyloxy)phenyl]methyl]acetamideand 2.24 g of 5-methylthiazole in 40 ml of toluene is refluxed for 4hours, cooled and diluted with 60 ml of ether and allowed to stand atroom temperature overnight. The solid is collected by centrifugation andwashed three times with ether then vacuum dried to give 3.1 g of thedesired product as a white powder, m.p. 130°-134° C.

EXAMPLE 33 p-(Tetradecyloxy)phenyl isocyanate

To a solution of 8.74 g of triphosgene in 125 ml of methylene chloridecooled to 0° C. is added dropwise a solution ofp-(tetradecyloxy)aniline, 7.95 g of triethylamine and 239.93 mg ofdimethylaminopyridine in 125 ml of methylene chloride over 30 minutes.Stirring at ambient temperature is continued for 4 hours. The solvent isevaporated and the residue stirred with ether and filtered. The cake iswashed with additional ether and the combined filtrates evaporated togive the desired product as an oil.

EXAMPLE 34 N-[3-(Hydroxymethyl)phenyl]-N'-[4-(tetradecyloxy)phenyl]urea

To a 0° C. solution of 13 g of p-(tetradecyloxy)phenyl isocyanate in 70ml of tetrahydrofuran and 30 ml of pyridine is added over 10 minutes asolution of 7.24 g of 3-aminobenzyl alcohol in 70 ml of tetrahydrofuranwith continued stirring for one hour. The mixture is heated until allthe solids dissolve then allowed to stand at ambient temperatureovernight. The mixture is poured into water and the solid collected. Thesolid is washed with dilute hydrochloric acid and Water thencrystallized from ethyl alcohol to give 13.1 g of the desired product asa light pink solid, m.p. 150°-158° C.

EXAMPLE 35 N-[3-(Bromomethyl)phenyl]-N'-[4-(tetradecyloxy)phenyl]urea

A mixture of 10.0 g ofN-[3-(hydroxymethyl)phenyl]-N'-[4-(tetradecyloxy)phenyl]urea, 70 ml ofhydrogen bromide in acetic acid and 40 ml of chloroform is refluxed for2.5 hours, then cooled. The solid is collected and washed with carbontetrachloride and two times with water. The collected solid iscrystallized from ethyl alcohol:tetrahydrofuran followed byrecrystallization from tetrahydrofuran to give 7.4 g of the desiredproduct as a white powder, m.p. 164°-169° C.

EXAMPLE 365-Methyl-3-[[3-[[[[4-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazoliumbromide

A mixture of 4 g ofN-[3-(bromomethyl)phenyl]-N'-[4-(tetradecyloxy)phenyl]urea and 2.3 g of5-methylthiazole in 60 ml of tetrahydrofuran is refluxed for 4 hours.The solvent is evaporated, toluene added to the residue and evaporatedto a residue. The residue is stirred with ether and the solid collected,washed with fresh ether and dried under vacuum to give 4.7 g of thedesired product as a white powder, m.p. 165°-168° C.

According to the methods outlined hereinabove in Flowsheet I anddescribed in detail in Examples 33-36, the compounds of this inventionlisted herein-below in List 3 can be prepared. These methods areapplicable to the preparation of the compounds of this invention by oneskilled in the art.

List 3

3-[[2-[[[[-4-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

3-[[2-[[[[3-methoxy-4-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

3-[[2-[[[[3-methoxy-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

3-[[2-[[[[2-chloro-4-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

3-[[2-[[[[4-chloro-3-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

3-[[2-[[[[4-t-butyl-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

3-[[2-[[[[4-methoxy-3-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

3-[[2-[[[[4-methoxy-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

3-[[3-[[[[-4-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

3-[[3-[[[[-3-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

3-[[3-[[[[3-chloro-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

3-[[3-[[[[3-fluoro-4-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

3-[[3-[[[[3-fluoro-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

3-[[3-[[[[3-methoxy-4-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

3-[[3-[[[[3-methoxy-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

3-[[3-[[[[2-chloro-4-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[[-3-(hexadecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[[-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[[-2-(hexadecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[[3-chloro-4-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[[3-chloro-4-(hexadecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[[3-chloro-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[[3-acetyl-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[[3-acetyl-2-(hexadecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[[3-t-butyl-4-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[[3-t-butyl-4-(hexadecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[[3-t-butyl-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[[3-methoxy-4-(hexadecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[[3-methoxy-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[[3-methoxy-2-(hexadecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[[2-chloro-4-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[[-4-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[[-3-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[[-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[[3-chloro-4-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[[3-chloro-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[[3-fluoro-4-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[[3-fluoro-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[[3-acetyl-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[[3-t-butyl-4-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[[3-t-butyl-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[[3-methoxy-4-(tetradecyloxy)phenyl]amino]carbonyl]amino]Phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[[3-methoxy-2-(tetradecyloxy)phenyl]amino]carbonyl)amino]Phenyl)methyl]thiazolium bromide

5-Methyl-3-[[2-[[[[2-chloro-4-(tetradecyloxy)phenyl]amino]carbonyl)amino]Phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[[4-chloro-3-(tetradecyloxy)phenyl]amino]carbonyl]amino]Phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[[4-t-butyl-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]Phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[[3-chloro-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]Phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[[3-chloro-2-(dodecyloxy)phenyl]amino]carbonyl]amino]Phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[[3-fluoro-4-(tetradecyloxy)phenyl]amino]carbonyl]amino]Phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[[3-fluoro-4-(dodecyloxy)phenyl]amino]carbonyl]amino]Phenyl]methyl)thiazolium bromide

5-Methyl-3-[[3-[[[[3-fluoro-2-(tetradecyloxy)phenyl)amino]carbonyl]amino]Phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[[3-fluoro-2-(dodecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[[3-acetyl-4-(tetradecyloxy)phenyl]amino]carbonyl]amino]Phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[[3-acetyl-4-(dodecyloxy)phenyl)amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[[3-acetyl-2-(tetradecyloxy)phenyl]amino]carbonyl)amino)phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[[3-t-butyl-4-(dodecyloxy)phenyl]amino]carbonyl]amino]Phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[[2-chloro-4-(tetradecyloxy)phenyl)amino]carbonyl]amino]phenyl]methyl)thiazolium bromide

5-Methyl-3-[[3-[[[[4-chloro-3-(dodecyloxy)phenyl]amino]carbonyl]amino]phenyl)methyl)thiazolium bromide

5-Methyl-3-[[3-[[[[4-chloro-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]Phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[[4-chloro-2-(dodecyloxy)phenyl]amino]carbonyl]amino]Phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[[4-t-butyl-3-(decyloxy)phenyl]amino]carbonyl]amino]Phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[[4-methoxy-3-(hexadecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[[4-methoxy-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[[4-methoxy-2-(dodecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[[-4-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[[-3-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[[-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[[3-acetyl-4-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[[3-acetyl-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[[3-t-butyl-4-(decyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[[3-t-butyl-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[[3-methoxy-4-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[[3-methoxy-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[[2-chloro-4-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[[4-chloro-3-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[[4-chloro-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[[4-t-butyl-3-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[[4-t-butyl-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[[4-methoxy-3-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[[4-methoxy-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[[[-4-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[[[2-chloro-4-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[[[4-chloro-3-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[[[4-chloro-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[[[4-t-butyl-3-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[[[4-methoxy-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[[-4-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[[-3-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[[-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[[3-chloro-4-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[[3-chloro-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[[3-fluoro-4-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[[3-fluoro-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[[2-chloro-4-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[[4-t-butyl-3-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[[[3-fluoro-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[[[3-acetyl-4-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[[[3-acetyl-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[[[3-methoxy-4-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[[[4-methoxy-3-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[[[4-methoxy-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[[-4-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[[-3-(tetradecyloxy)phenyl)amino)carbonyl]amino]Phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[[-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]Phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[[3-chloro-4-(tetradecyloxy)phenyl]amino)carbonyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[[3-chloro-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]Phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[[3-fluoro-4-(tetradecyloxy)phenyl]amino]carbonyl]amino]Phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[[3-fluoro-2-(tetradecyloxy)phenyl]amino]carbonyl]amino)Phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[[3-acetyl-4-(tetradecyloxy)phenyl]amino]carbonyl]amino]Phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[[3-acetyl-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]Phenyl)methyl]thiazolium bromide

4-Methyl-3-[[2-[[[[3-t-butyl-4-(tetradecyloxy)phenyl)amino]carbonyl]amino)Phenyl)methyl]thiazolium bromide

4-Methyl-3-[[3-[[[[-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl)thiazolium bromide

4-Methyl-3-[[3-([[[3-chloro-4-(octyloxy)phenyl]amino]carbonyl]amino]Phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[[3-chloro-2-(tetradecyloxy)phenyl)amino)carbonyl)amino]Phenyl)methyl)thiazolium bromide

4-Methyl-3-[[3-[[[[3-fluoro-4-(tetradecyloxy)phenyl]amino)carbonyl)amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[[3-fluoro-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[[3-acetyl-4-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-([([3-acetyl-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[[3-t-butyl-4-(decyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[[3-t-butyl-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[[3-methoxy-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[[2-chloro-4-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[[4-chloro-3-(tetradecyloxy)phenyl]amino]carbonyl]amino]Phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[[4-chloro-2-(tetradecyloxy)phenyl]amino)carbonyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[[-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[[3-chloro-4-(tetradecyloxy)phenyl)amino]carbonyl]amino]phenyl]methyl)thiazolium bromide

4-Methyl-3-[[4-[[[[3-chloro-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[[3-methoxy-2-(tetradecyloxy)phenyl]amino]carbonyl]amino)phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[[2-chloro-4-(tetradecyloxy)phenyl]amino]carbonyl]amino]Phenyl]methyl)thiazolium bromide

4-Methyl-3-[[4-[[[[4-chloro-3-(dodecyloxy)phenyl]amino]carbonyl)amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[[4-chloro-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[[4-t-butyl-2-(tetradecyloxy)phenyl]amino]carbonyl]amino]phenyl]methyl]thiazolium bromide

EXAMPLE 37 4-Methyl-1-(3-nitrophenyl)-1H-imidazole

To a mixture of 112.9 g of m-fluoronitrobenzene and 65.69 g of4-methylimidazole in 1 liter of dimethylsulfoxide is added 58.51 g ofpotassium carbonate followed by heating under dry conditions at 110° C.for 39 hours. The reaction mixture is poured into 3.3 liters of waterand stored in a refrigerator for 2 days. The mixture is filtered and thecake washed with copious volumes of water followed by suction drying togive 25 g of brown solid. The solid is crystallized from ethyl acetateto give 15.0 g of the desired product as a beige solid, m.p. 119°-120°C. From the combined recrystallization filtrates is obtained 800 mg of5-methyl-1-(3-nitrophenyl)-1H-imidazole as a beige solid, m.p. 130°-132°C.

EXAMPLE 38 3-(4-Methyl-1H-imidazol-1-yl)benzenamine

A mixture of 14.6 g of 4-methyl-1-(3-nitrophenyl)-1H-imidazole, 766 mgof palladium black, 19.6 g of sodium formate, 12.8 ml of formic acid in300 ml of methyl alcohol is stirred for 18 hours under a hydrogenatmosphere. The mixture is filtered through diatomaceous earth and thefiltrate evaporated to a residue. The residue is partitioned betweensaturated potassium bicarbonate and chloroform. The organic layer isdried and evaporated to a residue which is dissolved in a minimum ofchloroform and passed through a pad of hydrous magnesium silicate. Thefiltrate is evaporated to a residue which is stirred with ether and theresulting solid filtered and air dried to give 10.3 g of the desiredproduct as a solid, m.p. 117°-119° C.

EXAMPLE 39N-[3-(2-Methyl-1H-imidazol-1-yl)phenyl-4-(tetradecyloxy)benzeneacetamide

To a solution of 2.8 g of p-tetradecyloxyphenylacetyl chloride in 30 mlof tetrahydrofuran is added a solution of 1.32 g of3-(2-methyl-1H-imidazol-1-yl) benzenamine and 2.41 g of pyridine in 30ml of tetrahydrofuran followed by stirring for 2 hours at ambienttemperature. The mixture is heated briefly to reflux then stirred atambient temperature for 2 hours. The solvent is evaporated to a residue.The residue is partitioned between chloroform and saturated sodiumbicarbonate. The organic layer is dried and evaporated to an oil whichis chromatographed on silica gel using ethyl acetate:5% methylalcohol:0.l% ammonium hydroxide to give a solid which is crystallizedfrom hexane:carbon tetrachloride to give 2.6 g of the desired compoundas a white solid, m p. 110°-112° C.

EXAMPLE 40N-[3-(2-Methyl-1H-imidazol-1-yl)phenyl-4-(tetradecyloxy)benzeneacetamidemonohydrochloride

To a solution of 500 mg ofN-[3-(2-methyl-1H-imidazol-1-yl)phenyl-4-(tetradecyloxy)benzeneacetamidein a minimum of ether is treated with 70 ml of ether saturated withhydrogen chloride. The resulting solid is collected via centrifugation,washed with ether and vacuum dried to give 0.4 g of the desired productas a white solid, m.p. 175°-178° C.

EXAMPLE 412,3-Dimethyl-1-[3-[[[4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]-1H-imidazoliumiodide

A mixture of 800 mg ofN-[3-(2-methyl-1H-imidazol-1-yl)phenyl-4-(tetradecyloxy)benzeneacetamideand 1.13 g of methyl iodide in 15 ml of toluene is refluxed for 2.5hours. The solvent is evaporated to a residue which is stirred withether and the solid collected by centrifugation, washed with ether andvacuum dried to give 0.8 g of the desired product as a solid, m.p.140°-143° C.

EXAMPLE 42 2-Methyl-1-(p-nitrophenyl)imidazole

A mixture of 50.0 g of p-fluoronitrobenzene, 85.93 g of2-methylimidazole and 44.9 g of potassium carbonate in 860 ml ofdimethylsulfoxide is heated at 120° C. for 24 hours. The mixture ispoured into 2.5 liter of water and stored in a refrigerator for twodays. The mixture is filtered and cake washed with copious volumes ofwater and vacuum dried. The cake is dissolved in 1500 ml of ethylacetate, filtered through hydrous magnesium silicate and the filtratereduced to about 500 ml, cooled and the resulting solid, filtered, andair dried to give 81.0 g of the desired product as brown crystals, m.p.135°-137° C.

EXAMPLE 43 4-(2-Methyl-1H-imidazol-1-yl)benzenamine

A mixture of 54.0 g of 2-methyl-1-(p-nitrophenyl)imidazole, 2.87 g ofpalladium black, 36.7 g of sodium formate and 47.4 ml of formic acid in1100 ml of methyl alcohol is stirred at room temperature for 18 hoursunder a hydrogen atmosphere. The mixture is filtered and the filtrateevaporated to a residue. The residue is partitioned between saturatedpotassium bicarbonate and chloroform. The organic layer is dried andpassed through a pad of hydrous magnesium silicate. The filtrate isevaporated to a residue which is crystallized from ether:ethanol to give34.9 g of the desired product as a solid, m.p. 108°-110° C.

EXAMPLE 44N-[4-(2-Methyl-1H-imidazol-1-yl)phenyl]-4-(tetradecyloxy)benzeneacetamide

To a solution of 5.0 g of p-tetradecyloxyphenylacetyl chloride in 50 mlof tetrahydrofuran is added to a solution of 4.31 g of pyridine and 2.36g of 4-(2-methyl-1H-imidazol-1-yl)benzenamine in 50 ml oftetrahydrofuran over 5 minutes. The mixture is stirred at ambienttemperature for 1 hour, heated to reflux and allowed to stir at roomtemperature for 2 hours. The solvent is evaporated to a residue which ispartitioned between chloroform and dilute sodium bicarbonate. Theorganic layer is separated, washed with water, dried and filteredthrough a pad of magnesium silicate. The solvent is evaporated to an oilwhich crystallizes from methyl alcohol:water to give 4.0 g of whitesolid which is chromatographed on silica gel using ethyl acetatecontaining 0.1% ammonium hydroxide to give 3.9 g of the desired productas a white solid, m.p. 106°-109° C.

EXAMPLE 45N-[4-(2-Methyl-1H-imidazol-1-yl)phenyl]-4-(tetradecyloxy)benzeneacetamidemonohydrochloride

A solution of 500 mg ofN-[4-(2-methyl-1H-imidazol-1-yl)phenyl]-4-(tetradecyloxy)benzeneacetamidein 7 ml of tetrahydrofuran and 70 ml of ether is saturated with hydrogenchloride. The solid is collected by centrifugation, washed three timeswith ether and vacuum dried to give 0.5 g of the desired product as awhite solid, m.p. 207°-211° C.

EXAMPLE 462,3-Dimethyl-1-[4-[[[4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]-1H-imidazoliumiodide

A mixture of 1.5 g ofN-[4-(2-methyl-1H-imidazol-1-yl)phenyl]-4-(tetradecyloxy)benzeneacetamideand 2.11 g of methyl iodide in 25 ml of toluene is refluxed under argonfor 2 hours, cooled, diluted with ether and the solid collected. Thecake is dried to give 1.8 g of the desired product as a white solid,m.p. 140°-143° C.

EXAMPLE 47 p-(Hexadecyloxy)phenol

To a suspension of 28.99 g of 60% sodium hydride in 350 ml ofN,N-dimethylformamide, cooled to 0° C. and under argon is added 60 g ofhydroquinone in 450 ml of N,N-dimethylformamide with stirring over 40minutes. After an additional 30 minutes, 450 ml of tetrahydrofuran isadded followed by 192 g of 1-iodohexadecane over one hour. The mixtureis stirred at room temperature for 3 hours. The reaction mixture ispoured into dilute hydrochloric acid and extracted with chloroform. Theorganic layer is washed with water, dried and evaporated to give thedesired product as an oil.

EXAMPLE 48 4-Hexadecyloxyphenoxyacetic acid methyl ester

A mixture of 23 g of p-(hexadecyloxy)phenol, 13.35 g of methylbromoacetate, 10.45 g of potassium carbonate in 200 ml of acetone isrefluxed for 24 hours. The mixture is cooled, chloroform added andfiltered. The filtrate is evaporated and the residue crystallized fromhexane to give 25 g of the desired compound as a gray white solid.

EXAMPLE 49 [4-(Hexadecyloxy)phenoxy]acetic acid

A mixture of 24.5 g of 4-Hexadecyloxyphenoxyacetic acid methyl ester10.14 g of potassium hydroxide in 10 ml of water and 250 ml ethylalcohol is refluxed for 3 hours then allowed to stand at 50° for 18hours. The mixture is poured into dilute hydrochloric acid and extractedwith chloroform. The organic layer is evaporated to a residue which iscrystallized from hexane:carbon tetrachloride to give 13.7 g of thedesired product as a white solid, m.p. 125°-127° C.

EXAMPLE 50 4-Hexadecyloxyphenoxyacetyl chloride

A mixture of 13.2 g of [4-(hexadecyloxy)phenoxy]acetic acid, 6.4 g ofoxalyl chloride, 225 ml of methylene chloride and 5 drops ofN,N-dimethylformamide is stirred at ambient temperature for 17 hours.The solvent is evaporated to a residue which is dissolved in ether andfiltered through diatomaceous earth. The filtrate is evaporated to give13.9 g of the desired product as a white solid.

EXAMPLE 512-[4-(Hexadecyloxy)phenoxy]-N-[3-hydroxymethyl)phenyl]acetamide

To a solution of 1.75 g of m-aminobenzyl alcohol and 3.46 g of pyridinein 60 ml of methylene chloride, cooled to 0° C., is added dropwise withstirring 4.5 g of 4-hexadecyloxyphenoxyacetyl chloride in 60 ml ofmethylene chloride over 30 minutes. Stirring is continued for 4 hours.The mixture is diluted with chloroform and poured into water. Theorganic layer is washed with dilute hydrochloric acid, dried andevaporated to a residue which is crystallized from carbon tetrachlorideto give 5.1 g of the desired product as a white solid, m.p. 88°-91° C.

EXAMPLE 52N-[3-(Bromomethyl)phenyl]-2-[4-(hexadecyloxy)phenoxy]acetamide

To a solution of 3.5 g of2-[4-(hexadecyloxy)phenoxy]-N-[3-hydroxymethyl)phenyl]acetamide and 1.29g of methanesulfonyl chloride in 60 ml of tetrahydrofuran is added853.89 mg of triethylamine followed by stirring at room temperature for2.5 hours. Stirring is continued for 4 hours after adding 6.11 g oflithium bromide. The mixture is poured into water and extracted withether. The organic layer is washed with saturated sodium bicarbonate,dried and evaporated to a residue which is crystallized from hexane togive a solid which is chromatographed on silica gel with chloroform togive a solid which is crystallized from hexane to give 2.1 g of thedesired product as a white solid, m.p. 183°-186° C.

EXAMPLE 533-[[3-[[[4-(Hexadecyloxy)phenoxy]acetyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

A mixture of 1.9 g ofN-[3-(bromomethyl)phenyl]-2-[4-(hexadecyloxy)phenoxy]acetamide and 1.68g of 5-methyl thiazole in 25 ml of toluene is refluxed under argon for5.5 hours then concentrated to a residue which is mixed with ether andthe solid collected by centrifugation then washed several times withether. The solid is vacuum dried to give 1.7 g of the desired product asa white solid, m.p. 121°-124° C.

EXAMPLE 542-[4-(Hexadecyloxy)phenoxy]-N-[2-(hydroxymethyl)phenyl]acetamide

To a solution of 1.36 g of O-aminobenzyl alcohol and 2.69 g of pyridinein 60 ml of methylene chloride is added dropwise with stirring over 40minutes a solution of 3.5 g of 4-hexadecyloxyphenoxyacetyl chloride in40 ml of methylene chloride. Stirring is continued at room temperaturefor 4 hours. The mixture is diluted with chloroform and heated todissolve the solids, washed with water and dilute hydrochloric acid. Theorganic layer is dried and evaporated to a residue which is crystallizedfrom carbon tetrachloride to give 3.9 g of the desired product as awhite solid, m.p. 128°-131° C.

EXAMPLE 55N-[2-(Bromomethyl)phenyl]-2-[4-(hexadecyloxy)phenoxy]acetamide

To a solution of 3.5 g of2-[4-(hexadecyloxy)phenoxy]-N-[2-(hydroxymethyl)phenyl]acetamide and1.29 g of methanesulfonyl chloride in 60 ml of tetrahydrofuran is added853.89 mg of triethylamine followed by stirring at room temperature for2.5 hours. Also added is 6.11 g of lithium bromide followed by stirringat room temperature for 4 hours. The mixture is poured into water andextracted with ether. The organic layer is dried and passed through apad of magnesium silicate. The solvent is evaporated to a residue whichis crystallized from hexane to give 2.0 g of the desired product as awhite solid.

EXAMPLE 563-[[2-[[[4-(Hexadecyloxy)phenoxy]acetyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

A mixture of 1.8 g ofN-[2-(bromomethyl)phenyl]-2-[4-(hexadecyloxy)phenoxy]acetamide and 1.59g of 5-methyl thiazole in 25 ml of toluene is refluxed under argon for 6hours. The solvent is evaporated to a residue which is stirred withether and the solid collected by centrifugation, washed with ether andvacuum dried to give 1.7 g of the desired product as an off-white solid,m.p. 121°-124° C.

According to the methods outlined hereinabove in Flowsheet F anddescribed in detail in Examples 47-56, the compounds of this inventionlisted hereinbelow in List 4 can be prepared. These methods areapplicable to the preparation of the compounds of this invention by oneskilled in the art.

List 4

3-[[2-[[[-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[2-[[[-3-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[2-[[[-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[2-[[[3-chloro-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[2-[[[3-fluoro-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[2-[[[3-t-butyl-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[2-[[[3-methoxy-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[2-[[[3-methoxy-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[2-[[[2-chloro-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[2-[[[4-chloro-3-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[2-[[[4-t-butyl-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[2-[[[4-methoxy-3-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[2-[[[4-methoxy-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[3-[[[-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[3-[[[-3-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[3-[[[3-chloro-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[3-[[[3-fluoro-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[3-[[[3-fluoro-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[3-[[[3-methoxy-4-(tetradecyloxy)phenoxy)acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[3-[[[3-methoxy-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[3-[[[2-chloro-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[3-[[[4-t-butyl-3-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[3-[[[4-t-butyl-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[3-[[[4-methoxy-3-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[-4-(hexadecyloxy) phenoxy]acetyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[[[-3-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[-3-(hexadecyloxy) phenoxy]acetyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[[[-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[-2-(hexadecyloxy) phenoxy]acetyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[[[3-chloro-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[3-chloro-4-(hexadecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[3-chloro-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[3-acetyl-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[3-acetyl-2-(hexadecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[3-t-butyl-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[3-t-butyl-4-(hexadecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[3-t-butyl-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[3-methoxy-4-(hexadecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[3-methoxy-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[3-methoxy-2-(hexadecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[2-chloro-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[2-chloro-4-(hexadecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[4-chloro-3-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[4-chloro-3-(hexadecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[4-chloro-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

3-[[4-[[[4-t-butyl-3-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[-3-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[3-chloro-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[3-chloro-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[3-fluoro-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[3-fluoro-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[3-acetyl-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[3-t-butyl-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[3-t-butyl-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[3-methoxy-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[3-methoxy-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[2-chloro-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[4-chloro-3-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[4-t-butyl-2-(tetradecyloxy)phenoxy]acetyl)amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[([4-methoxy-3-(tetradecyloxy)phenoxy]acetyl)amino]Phenyl)methyl]thiazolium bromide

5-Methyl-3-[[3-[[[-3-(dodecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[-2-(dodecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[3-chloro-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[3-chloro-2-(dodecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[3-fluoro-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[3-fluoro-4-(dodecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[3-fluoro-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[3-fluoro-2-(dodecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[3-acetyl-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[3-acetyl-4-(dodecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[3-acetyl-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[3-t-butyl-4-(dodecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[2-chloro-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[4-chloro-3-(dodecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[4-chloro-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[4-chloro-2-(dodecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[4-t-butyl-3-(decyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[4-t-butyl-3-(dodecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[4-t-butyl-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[4-t-butyl-2-(dodecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[4-methoxy-3-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[4-methoxy-3-(dodecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[4-methoxy-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[4-methoxy-2-(dodecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[-3-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[3-acetyl-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[3-acetyl-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[3-t-butyl-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[3-t-butyl-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[3-methoxy-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[3-methoxy-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[2-chloro-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[4-chloro-3-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[4-chloro-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[4-t-butyl-3-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[4-t-butyl-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[4-methoxy-3-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[4-methoxy-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[[-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[[3-chloro-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[[3-t-butyl-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[[3-methoxy-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[[3-methoxy-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[[2-chloro-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[[4-chloro-3-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[[4-chloro-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[[4-t-butyl-3-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[[4-methoxy-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[-3-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[3-chloro-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[3-chloro-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[3-fluoro-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[3-fluoro-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[2-chloro-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[4-t-butyl-3-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[4-t-butyl-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[4-methoxy-3-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[4-methoxy-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[[-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[[-3-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[[-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[[3-chloro-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[[3-chloro-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[[3-fluoro-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[[3-fluoro-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[[3-acetyl-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[[3-acetyl-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[[3-methoxy-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[[4-methoxy-3-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[[4-methoxy-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[-3-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[3-chloro-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[3-chloro-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[3-fluoro-4-(tetradecyloxy)phenoxy)acetyl)amino]Phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[3-fluoro-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[3-acetyl-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[3-acetyl-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[3-t-butyl-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[3-t-butyl-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[3-methoxy-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[3-methoxy-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[4-methoxy-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[3-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[3-chloro-4-(octyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[3-chloro-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[3-fluoro-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[3-fluoro-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[3-acetyl-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[3-acetyl-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[3-t-butyl-4-(decyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[3-t-butyl-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[3-methoxy-2-(tetradecyloxy)phenoxy]acetyl]amino]Phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[2-chloro-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[4-chloro-3-(tetradecyloxy)phenoxy)acetyl)amino]phenyl)methyl]thiazolium bromide

4-Methyl-3-[[3-[[[4-chloro-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[3-chloro-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[3-chloro-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[3-fluoro-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromidephenoxy]acetyl[4-[[[3-acetyl-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[3-acetyl-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[3-t-butyl-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[3-t-butyl-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[3-methoxy-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[3-methoxy-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[2-chloro-4-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[4-chloro-3-(dodecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[4-chloro-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[4-t-butyl-2-(tetradecyloxy)phenoxy]acetyl]amino]phenyl]methyl]thiazolium bromide

EXAMPLE 57 3-[[2-[4-(Tetradecyloxy)phenyl]ethyl]aminobenzenemethanol

To a solution of 42.36 ml of 1 molar lithium aluminum hydride in eitheris added dropwise under argon over 20 minutes a solution of ethyl3-[[[4-(tetradecyloxy)phenyl]acetyl]amino]benzoate in 50 ml of eitherand 50 ml of tetrahydrofuran. The mixture is refluxed for 3 hours,cooled to 0° C. and ethyl acetate added. Saturated sodium sulfate isadded followed by ether. The mixture is filtered and the cake washedwith ether. The filtrate is evaporated and the residue chromatographedon silica gel using 9:1 chloroform:ethyl acetate. The product fractionsare combined and evaporated to a residue which is crystallized fromhexane to give 4.5 g of the desired product as a white solid, m.p.67°-70° C.

EXAMPLE 58N-[3-(Bromomethyl)phenyl-N-[2-[4-(tetradecyloxy)phenyl]ethyl]acetamide

A mixture of 4 g of3-[[2-[4-(tetradecyloxy)phenyl]ethyl]aminobenzenemethanol, 3.71 g ofacetic anhydride and 2.3 g of triethylamine in 50 ml of chloroform isrefluxed for 3 hours. The solvent is evaporated to a residue which ismixed with 15 ml of 30% HBr in acetic acid followed by heating at 80° C.for 2.5 hours. The mixture is poured into water and extracted withether. The organic layer is washed with saturated sodium bicarbonate,dried and evaporated to a residue which is crystallized from hexanes togive 4.4 g of the desired product as a white solid, m.p. 75°-77° C.

EXAMPLE 593-[[3-[Acetyl[2-[4-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

A mixture of 2.5 g ofN-[3-(bromoethyl)phenyl-N-[2-[4-(tetradecyloxy)phenyl]ethyl]acetamideand 2.28 g of 5-methylthiazole in 50 ml of toluene is refluxed for 5hours, cooled and ether added. The solid is collected by centrifugationand washed several times with ether then vacuum dried to give 1.8 g ofthe desired product as a white solid, m.p. 136°-140° C.

According to the methods outlined hereinabove in Flowsheet C anddescribed in detail in Examples 57-59, the compounds of this inventionlisted hereinbelow in List 5 can be prepared. These methods areapplicable to the preparation of the compounds of this invention by oneskilled in the art.

List 5

3-[[4-[acetyl[2-[4-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[acetyl[2-[4-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[4-[acetyl[2-[4-(dodecyloxy)phenyl]ethyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[acetyl[2-[4-(hexadecyloxy)phenyl]ethyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[4-[acetyl[2-[3-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[acetyl[2-[3-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[4-[acetyl[2-[3-(dodecyloxy)phenyl]ethyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[acetyl[2-[3-(dodecyloxy)phenyl]ethyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[4-[acetyl[2-[3-chloro-4-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[acetyl[2-[3-chloro-4-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[4-[acetyl[2-[3-fluoro-4-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[acetyl[2-[3-fluoro-4-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[4-[acetyl[2-[3-t-butyl-4-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[acetyl[2-[3-t-butyl-4-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[4-[acetyl[2-[3-methoxy-4-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[acetyl[2-[3-methoxy-4-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[4-[acetyl[2-[4-chloro-3-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[acetyl[2-[4-chloro-3-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[4-[acetyl[2-[4-t-butyl-3-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[acetyl[2-[4-t-butyl-3-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[4-[acetyl[2-[4-methoxy-3-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[acetyl[2-[4-methoxy-3-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[3-[acetyl[2-[4-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]thiazoliumbromide

3-[[3-[acetyl[2-[4-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[3-[acetyl[2-[4-(hexadecyloxy)phenyl]ethyl]amino]phenyl]methyl]thiazoliumbromide

3-[[3-[acetyl[2-[4-(dodecyloxy)phenyl]ethyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[3-[acetyl[2-[3-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]thiazoliumbromide

3-[[3-[acetyl[2-[3-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[3-[acetyl[2-[3-(hexadecyloxy)phenyl]ethyl]amino]phenyl]methyl]thiazoliumbromide

3-[[3-[acetyl[2-[3-(hexadecyloxy)phenyl]ethyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[3-[acetyl[2-[3-chloro-4-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]thiazoliumbromide

3-[[3-[acetyl[2-[3-chloro-4-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[3-[acetyl[2-[3-chloro-4-(hexadecyloxy)phenyl]ethyl]amino]phenyl]methyl]thiazoliumbromide

3-[[3-[acetyl[2-[3-chloro-4-(hexadecyloxy)phenyl]ethyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[3-[acetyl[2-[3-fluoro-4-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]thiazoliumbromide

3-[[3-[acetyl[2-[3-fluoro-4-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[3-[acetyl[2-[3-t-butyl-4-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]thiazoliumbromide

3-[[3-[acetyl[2-[3-t-butyl-4-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[3-[acetyl[2-[3-methoxy-4-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]thiazoliumbromide

3-[[3-[acetyl[2-[3-methoxy-4-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[3-[acetyl[2-[4-chloro-3-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]thiazoliumbromide

3-[[3-[acetyl[2-[4-chloro-3-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl-5-methyl-thiazoliumbromide

3-[[3-[acetyl[2-[4-t-butyl-3-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]thiazoliumbromide

3-[[3-[acetyl[2-[4-t-butyl-3-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[3-[acetyl[2-[4-methoxy-3-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]thiazoliumbromide

3-[[3-[acetyl[2-[4-methoxy-3-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[3-[Propionyl[[4-methoxy-3-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[2-[acetyl[2-[4-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[2-[acetyl[2-[3-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[2-[acetyl[2-[3-chloro-4-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[2-[acetyl[2-[3-fluoro-4-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[2-[acetyl[2-[3-methoxy-4-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[2-[acetyl[2-[4-chloro-3-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[2-[acetyl[2-[4-methoxy-3-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

EXAMPLE 60N'-Methyl-N-[3-[[[(methylamino)carbonyl]oxy]methyl]phenyl]-N-[[4-(tetradecyloxy)phenyl]methyl]urea

A mixture of 8 g of3-[[[4-(tetradecyloxy)phenyl]methyl]aminobenzenemethanol and 3.22 g ofmethyl isocyanate in 10 ml of pyridine and 20 ml of ether is stirred atroom temperature overnight. The mixture is poured into water andextracted with ether:tetrahydrofuran. The organic layer is washed withdilute hydrochloric acid and brine. The organic layer is dried andevaporated to a residue which is crystallized from hexane:carbontetrachloride to give 8.7 g of the desired product as a white powder,m.p. 107°-109° C.

EXAMPLE 61N-[3-(Hydroxymethyl)phenyl]-N'-methyl-N-[4-(tetradecyloxy)phenyl]urea

A mixture of 7.8 g ofN'-methyl-N-[3-[[[(methylamino)carbonyl]oxy]methyl]phenyl]-N-[[4-(tetradecyloxy)phenyl]methyl]ureaand 768.77 mg of sodium hydroxide in 100 ml of ethyl alcohol and 10 mlof water is refluxed for 6 hours. The mixture is poured into water andextracted with ether:tetrahydrofuran. The organic layer is washed withbrine, dried and evaporated to a residue which is crystallized fromcarbon tetrachloride:hexane to give 6.9 g of the desired product as awhite solid.

EXAMPLE 62N-[3-(Bromomethyl)phenyl]-N'-methyl-N-[[4-(tetradecyloxy)phenyl]methyl]urea

To a solution ofN-[3-(hydroxymethyl)phenyl]-N'-methyl-N-[4-(tetradecyloxy)phenyl]ureaand 1.64 g of methanesulfonyl chloride in 100 ml of tetrahydrofuran isadded 1.45 g of triethylamine followed by stirring at room temperaturefor 1.5 hours. Added 10.8 g of lithium bromide and stirred at roomtemperature for 4 hours. The mixture is poured into water and extractedwith ether. The organic layer is dried and evaporated to a residue whichis purified by chromatography on silica gel using 3:1 hexane:ethylacetate to give 3.5 g of the desired product as a white solid, m.p.70°-73° C.

EXAMPLE 635-Methyl-3-[[3-[[(methylamino)carbonyl]-[[4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

A mixture of 3.3 g ofN-[3-(bromomethyl)phenyl]-N'-methyl-N-[[4-(tetradecyloxy)phenyl]methyl]ureaand 2.1 g of 5-methylthiazole in 50 ml of acetonitrile is refluxed underargon for 5 hours. The mixture is allowed to stand at room temperatureovernight. The mixture is diluted with ether and the solid collected.The solid is washed several times with ether then vacuum dried to give3.7 g of the desired product as a white solid, m.p. 124°-126° C.

According to the methods outlined hereinabove in Flowsheet C anddescribed in detail in Examples 60-63, the compounds of this inventionlisted hereinbelow in List 6 can be prepared. These methods areapplicable to the preparation of the compounds of this invention by oneskilled in the art.

List 6

3-[[4-[[(methylamino)carbonyl][[4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[[(methylamino)carbonyl][[4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[4-[[(methylamino)carbonyl][[3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[[(methylamino)carbonyl][[3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[4-[[(methylamino)carbonyl][[3-(dodecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[[(methylamino)carbonyl][[3-(dodecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[4-[[(methylamino)carbonyl][[3-chloro-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[[(methylamino)carbonyl][[3-methoxy-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[4-[[(methylamino)carbonyl][[4-chloro-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[[(methylamino)carbonyl][[4-chloro-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[4-[[(methylamino)carbonyl][[4-t-butyl-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[[(methylamino)carbonyl][[4-t-butyl-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[4-[[(methylamino)carbonyl][[4-methoxy-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[[(methylamino)carbonyl][[4-methoxy-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[3-[[(methylamino)carbonyl][[4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[3-[[(methylamino)carbonyl][[4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[3-[[(methylamino)carbonyl][[3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[3-[[(methylamino)carbonyl][[3-t-butyl-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[3-[[(methylamino)carbonyl][[3-methoxy-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[3-[[(methylamino)carbonyl][[3-methoxy-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[3-[[(methylamino)carbonyl][[4-chloro-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[3-[[(methylamino)carbonyl][[4-chloro-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[3-[[(methylamino)carbonyl][[4-t-butyl-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[3-[[(methylamino)carbonyl][[4-t-butyl-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[3-[[(methylamino)carbonyl][[4-methoxy-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[3-[[(methylamino)carbonyl][[4-methoxy-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

EXAMPLE 641-[[3-[Acetyl[[4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,4-dimethylpyridiniumbromide

A mixture of 1.6 g ofN-[3-(bromomethyl)phenyl]-N-[[4-(tetradecyloxy)phenyl]methyl]acetamideand 1.29 g of 3,4-lutidine in 25 ml of acetonitrile is refluxed underargon for 5 hours. The solvent is evaporated and the residue stirredwith ether. The solid is collected by centrifugation, washed severaltimes with ether and vacuum dried to give the desired product as asolid, m.p. 100°-103° C.

EXAMPLE 651-[[4-[Acetyl[[4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,4-dimethylpyridiniumbromide

A mixture of 1.5 g ofN-[4-(bromomethyl)phenyl]-N-[[4-(tetradecyloxy)phenyl]methyl]acetamideand 908.82 mg of 3,4-lutidine in 25 ml of acetonitrile is refluxed for 5hours. The solvent is evaporated, the residue stirred with ether and thesolid collected by centrifugation. The solid is washed with ether andvacuum dried to give 1.3 g of the desired product as a gummy solid, m.p.124°-127° C.

EXAMPLE 663,5-Dimethyl-1-[[3-[[[4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridiniumbromide

A mixture of 1.5 g ofN-[3-(bromomethyl)phenyl]-4-(tetradecyloxy)benzeneacetamide and 933.5 mgof 3,5-lutidine is refluxed in 25 ml of acetonitrile for 4 hours underargon. The solvent is evaporated and the residue stirred with ether andcollected by centrifugation. The solid is washed several times withether and vacuum dried to give 1.6 g of the desired product as a whitepowder, m.p. 122°-125° C.

EXAMPLE 673,4-Dimethyl-1-[[3-[[[4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridiniumbromide

A mixture of 1.5 g ofN-[3-(bromomethyl)phenyl]-4-(tetradecyloxy)benzeneacetamide and 933.5 mgof 3,4-lutidine in 25 ml of acetonitrile is refluxed under argon for 4hours. The solvent is evaporated and the residue mixed with ether. Thesolid is collected via centrifugation, washed with ether several timesand vacuum dried to give 1.5 g of the desired product as a gray-whitepowder, m.p. 125°-128° C.

EXAMPLE 682-[[3-[[[4-(Tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]imidazo[1,5-a]pyridiniumbromide

A mixture of 1.5 g ofN-[3-(bromomethyl)phenyl]-4-(tetradecyloxy)benzeneacetamide and 1.03 gof imidazo[l,2-a]pyridine in 25 ml of acetonitrile is refluxed underargon for 3.5 hours. The solvent is evaporated and the residue stirredwith ether and collected by centrifugation. The solid is washed severaltimes with ether and vacuum dried to give 1.5 g of the desired productas a white powder, m.p. 133°-135° C.

According to the methods outlined hereinabove in Flowsheet A anddescribed in detail in Examples 66-68, the compounds of this inventionlisted hereinbelow in List 7 can be prepared. These methods areapplicable to the preparation of the compounds of this invention by oneskilled in the art.

List 7

2-[[2-[[[-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]imidazo[1,5-a]pyridinium bromide

2-[[2-[[[-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]imidazo[1,5-a]pyridinium bromide

2-[[2-[[[-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]imidazo[1,5-a]pyridinium bromide

2-[[2-[[[3-chloro-4-(hexadecyloxy)phenyl]acetyl]amino]phenyl]methyl]imidazo[1,5-a]pyridinium bromide

2-[[2-[[[3-acetyl-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]imidazo[1,5-a]pyridinium bromide

2-[[2-[[[3-acetyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]imidazo[1,5-a]pyridinium bromide

2-[[2-[[[3-t-butyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]imidazo[1,5-a]pyridinium bromide

2-[[2-[[[3-methoxy-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]imidazo[1,5-a]pyridinium bromide

2-[[2-[[[2-chloro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]imidazo[1,5-a]pyridinium bromide

2-[[2-[[[4-chloro-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]imidazo[1,5-a]pyridinium bromide

2-[[2-[[[4-t-butyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]imidazo[1,5-a]pyridinium bromide

2-[[2-[[[4-methoxy-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]imidazo[1,5-a]pyridinium bromide

2-[[2-[[[4-methoxy-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]imidazo[1,5-a]pyridinium bromide

2-[[2-[[[-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]imidazo[1,5-a]pyridinium bromide

2-[[2-[[[-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]imidazo[1,5-a]pyridinium bromide

2-[[2-[[[3-chloro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]imidazo[1,5-a]pyridinium bromide

2-[[2-[[[3-fluoro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]imidazo[1,5-a]pyridinium bromide

2-[[2-[[[3-fluoro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]imidazo[1,5-a]pyridinium bromide

2-[[2-[[[3-acetyl-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]imidazo[1,5-a]pyridinium bromide

2-[[2-[[[3-acetyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]imidazo[1,5-a]pyridinium bromide

2-[[2-[[[3-t-butyl-4-(tetradecyloxy)phenyl]acetyl]amino]Phenyl]methyl]imidazo[1,5-a]pyridinium bromide

2-[[2-[[[3-t-butyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]imidazo[1,5-a]pyridinium bromide

2-[[2-[[[3-methoxy-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]imidazo[1,5-a]pyridinium bromide

2-[[2-[[[3-methoxy-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]imidazo[1,5-a]pyridinium bromide

2-[[2-[[[2-chloro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]imidazo[1,5-a]pyridinium bromide

2-[[2-[[[4-t-butyl-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]imidazo[1,5-a]pyridinium bromide

2-[[2-[[[4-t-butyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]imidazo[1,5-a]pyridinium bromide

2-[[2-[[[4-methoxy-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]imidazo[1,5-a]pyridinium bromide

2-[[4-[[[-4-(hexadecyloxyphenyl]acetyl]amino]phenyl]methyl]imidazo[1,5-a]pyridinium bromide

2-[[4-[[[-4-(hexadecyloxy)phenyl]acetyl]amino]phenyl]methyl]imidazo[1,5-a]pyridinium bromide

1-[[2-[[[-4-(tetradecyloxy) phenyl]acetyl]amino]phenyl]methyl]pyridiniumbromide

1-[[2-[[[-3-(tetradecyloxy) phenyl]acetyl]amino]phenyl]methyl]pyridiniumbromide

1-[[2-[[[-2-(tetradecyloxy) phenyl]acetyl]amino]phenyl]methyl]pyridiniumbromide

1-[[2-[[[3-chloro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

1-[[2-[[[3-fluoro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

1-[[2-[[[3-acetyl-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

1-[[2-[[[3-acetyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

1-[[2-[[[3-t-butyl-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

1-[[2-[[[3-t-butyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

1-[[2-[[[3-methoxy-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

1-[[2-[[[3-methoxy-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

1-[[2-[[[2-chloro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]Pyridinium bromide

1-[[2-[[[4-chloro-3-(tetradecyloxy)phenyl]acetyl]amino)phenyl]methyl]pyridinium bromide

1-[[2-[[[4-t-butyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

1-[[2-[[[4-methoxy-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

1-[[2-[[[4-methoxy-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

1-[[1-[[[-4-(tetradecyloxy) phenyl]acetyl]amino]phenyl]methyl]pyridiniumbromide

1-[[1-[[[-3-(tetradecyloxy) phenyl]acetyl]amino]phenyl]methyl]pyridiniumbromide

1-[[1-[[[3-chloro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

1-[[1-[[[3-fluoro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

1-[[1-[[[3-fluoro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

1-[[1-[[[3-acetyl-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

1-[[1-[[[3-acetyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

1-[[1-[[[3-t-butyl-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

1-[[4-[[[3-fluoro-2-(hexadecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

1-[[4-[[[3-acetyl-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

1-[[4-[[[3-acetyl-4-(hexadecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

1-[[4-[[[3-acetyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

1-[[4-[[[3-acetyl-2-(hexadecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

1-[[4-[[[3-t-butyl-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

1-[[4-[[[3-t-butyl-4-(hexadecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

1-[[4-[[[3-t-butyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

1-[[4-[[[3-methoxy-4-(hexadecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

1-[[4-[[[3-methoxy-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

1-[[4-[[[3-methoxy-2-(hexadecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

1-[[4-[[[2-chloro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

1-[[4-[[[2-chloro-4-(hexadecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

1-[[4-[[[4-chloro-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

1-[[4-[[[4-chloro-3-(hexadecyloxy)phenyl]acetyl]amino)phenyl]methyl]pyridinium bromide

1-[[4-[[[4-chloro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

1-[[4-[[[4-t-butyl-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

1-[[4-[[[4-t-butyl-3-(hexadecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

1-[[4-[[[4-t-butyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

1-[[4-[[[4-t-butyl-2-(hexadecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

1-[[4-[[[4-methoxy-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

1-[[4-[[[4-methoxy-3-(hexadecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

3,4-Dimethyl-1-[[2-[[[-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

3,4-Dimethyl-1-[[2-[[[-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

3,4-Dimethyl-1-[[2-[[[-2-(hexadecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

3,4-Dimethyl-1-[[2-[[[3-chloro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

3,4-Dimethyl-1-[[2-[[[3-fluoro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

3,4-Dimethyl-1-[[2-[[[3-acetyl-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

3,4-Dimethyl-1-[[2-[[[3-acetyl-2-(tetradecyloxy)phenyl]acetyl)amino)phenyl]methyl]pyridinium bromide

3,4-Dimethyl-1-[[2-[[[3-t-butyl-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

3,4-Dimethyl-1-[[2-[[[3-t-butyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

3,4-Dimethyl-1-[[2-[[[3-methoxy-4-(tetradecyloxy)phenyl]acetyl)amino]phenyl]methyl)pyridinium bromide

3,4-Dimethyl-1-[[2-[[[3-methoxy-2-(tetradecyloxy)phenyl]acetyl]amino]Phenyl]methyl]pyridinium bromide

3,4-Dimethyl-1-[[2-[[[2-chloro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

3,4-Dimethyl-1-[[3,4-Dimethyl-1-[[[3-acetyl-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

3,4-Dimethyl-1-[[3,4-Dimethyl-1-[[[3-acetyl-2-(tetradecyloxy)phenyl]acetyl]amino]Phenyl]methyl]pyridinium bromide

3,4-Dimethyl-1-[[3,4-Dimethyl-1-[[[3-t-butyl-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

3,4-Dimethyl-1-[[4-[[[3-fluoro-2-(tetradecyloxy)phenyl]acetyl]amino]Phenyl]methyl]Pyridinium bromide

3,4-Dimethyl-1-[[4-[[[3-acetyl-4-(tetradecyloxy)phenyl]acetyl]amino]Phenyl]methyl]pyridinium bromide

3,4-Dimethyl-1-[[4-[[[3-acetyl-4-(hexadecyloxy)phenyl]acetyl]amino]Phenyl]methyl]Pyridinium bromide

3,5-Dimethyl-1-[[2-[[[-4-(tetradecyloxy)phenyl]acetyl]amino]Phenyl]methyl]Pyridinium bromide

3,5-Dimethyl-1-[[2-[[[-3-(tetradecyloxy)phenyl]acetyl]amino]Phenyl]methyl]Pyridinium bromide

3,5-Dimethyl-1-[[2-[[[-2-(dodecyloxy)phenyl]acetyl]amino]Phenyl)methyl]Pyridinium bromide

3,5-Dimethyl-1-[[2-[[[3-chloro-4-(tetradecyloxy)phenyl]acetyl]amino]Phenyl]methyl)Pyridinium bromide

3,5-Dimethyl-1-[[2-[[[3-fluoro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]Pyridinium bromide

3,5-Dimethyl-1-[[2-[[[3-acetyl-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

3,5-Dimethyl-1-[[2-[[[3-acetyl-2-(tetradecyloxy)phenyl]acetyl)amino]phenyl]methyl]Pyridinium bromide

3,5-Dimethyl-1-[(2-[[[3-t-butyl-4-(tetradecyloxy)phenyl)acetyl]amino]phenyl]methyl]Pyridinium bromide

3,5-Dimethyl-1-[[2-[[[3-t-butyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

3,5-Dimethyl-1-[[2-[[[3-methoxy-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

3,5-Dimethyl-1-[[2-[[[3-methoxy-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

3,5-Dimethyl-1-[[2-[[[2-chloro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

3,5-Dimethyl-1-[[4-[[[2-chloro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

3,5-Dimethyl-1-[[4-[[[2-chloro-4-(hexadecyloxy)phenyl]acetyl]amino]phenyl]methyl]pyridinium bromide

EXAMPLE 69 2-(Trimethylstannyl)thiazole

To 99.99 ml of n-butyl lithium in hexane, dissolved in 200 ml of etheris added dropwise with stirring over 1 hour, at -78° C., a solution of16 g of thiazole in 100 ml of ether over 1 hour. A solution of 49.81 gof trimethyltin chloride in 100 ml of ether is added dropwise over 20minutes followed by additional stirring for 1 hour. The reaction mixtureis poured into saturated sodium bicarbonate and the organic layerseparated, dried and evaporated to a residue. The residue is vacuumdistilled to give 33.4 g of the desired product as a colorless liquid,B.P. 60°-65° C./0.7 mm.

EXAMPLE 70N-[2-[4-(Tetradecyloxy)phenyl]ethyl]-N-[3-(2-thiazolylmethyl)phenyl]acetamide

A mixture of 1.3 g ofN-[3-(bromomethyl)phenyl-N-[2-[4-(tetradecyloxy)phenyl]ethyl]acetamide,787.04 mg of 2-(trimethylstannyl)thiazole and 83.77 mg of PdCl₂ (PO)₂ in30 ml of tetrahydrofuran is stirred at reflux for 14 hours. The mixtureis diluted with ether and filtered through a pad of silica gel. Thefiltrate is washed with 1N sodium hydroxide, dried and filtered througha pad of alumina. The solvent is evaporated and the residuechromatographed on silica gel using 1:1 ethyl acetate:hexane to give 0.7g of the desired product as an oil which crystallized to an off-whitesolid, m.p. 46°-50° C.

EXAMPLE 71N-[2-[4-(Tetradecyloxy)phenyl]ethyl]-N-[3-(2-thiazolylmethyl)phenyl]acetamidemonohydrochloride

To a solution of 300 mg ofN-[2-[4-(tetradecyloxy)phenyl]ethyl]-N-[3-(2-thiazolylmethyl)phenyl]acetamidein 3 ml of ether is added 10 ml of ether saturated with hydrogenchloride. The resulting solid is collected by centrifugation, washedseveral times with ether and vacuum dried to give 200 mg of the desiredproduct, m.p. 114°-118° C.

EXAMPLE 723-Methyl-2-[[3-[acetyl[2-[4-(tetradecyloxy)phenyl]ethyl]amino]phenyl]methyl]thiazoliumiodide

A mixture of 300 mg ofN-[2-[4-(tetradecyloxy)phenyl]ethyl]-N-[3-(2-thiazolylmethyl)phenyl]acetamideand 1.4 g of methyl iodide in 5 ml of toluene is heated at 140° C. in aclosed vessel for 4.5 hours then cooled. Ether is added, the solidcollected by centrifugation and then washed several times with ether.The solid is vacuum dried to give 235 mg of the desired product as a tansolid, m.p. 130°-134° C.

EXAMPLE 73 N-(3-Iodophenyl)-4-(tetradecyloxy)benzeneacetamide

To a solution of 14.29 g of m-iodoaniline and 15.52 g of pyridine in 150ml of tetrahydrofuran is added at room temperature over 20 minutes asolution of p-tetradecyloxyphenylacetyl chloride in 150 ml oftetrahydrofuran. The mixture is stirred overnight and the solventremoved. The residue is partitioned between dilute hydrochloric acid andwarm chloroform. The separated organic layer is washed with dilutehydrochloric acid, dried and evaporated to a residue which iscrystallized from carbon tetrachloride:hexane to give 25.0 g of thedesired product as a pink solid, m.p. 108°-110° C.

EXAMPLE 74 4-(Tetradecyloxy)-N-[3-(2-thiazolyl)phenyl]benzeneacetamide

A mixture of 10 g of N-[3-iodophenyl)-4-(tetradecyloxy)benzeneacetamide,4.96 g of 2-(trimethylstannyl)thiazole, and 638.62 mg ofdichlorobis(triphenylphosphine)palladium (II) in 100 ml oftetrahydrofuran is refluxed under argon for 6 hours. The solvent isevaporated and the residue is partitioned between chloroform and 1Nsodium hydroxide. The organic layer is dried and evaporated to a yellowsolid residue. The residue is purified by chromatography on silica gelusing chloroform. A total of 3.5 g of starting material is recovered aswell as impure product which is crystallized from hexane:carbontetrachloride to give 1.8 g of the desired product as a tan solid, m.p.128°-131° C.

EXAMPLE 753-Methyl-2-[3-[[[4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazoliumchloride

A mixture of 1.4 g of4-(tetradecyloxy)-N-[3-(2-thiazolyl)phenyl]benzeneacetamide and 11.76 gof methyl iodide in 15 ml of acetonitrile is heated at 100° C. in aclosed glass vessel for 6 hours. The solvent is evaporated and theresidue dissolved in methyl alcohol and stirred with 12 g of chlorideion exchange resin, then filtered. The solvent is removed and theresidue dissolved in a minimum of methylene chloride and ether added.The resulting solid is collected by centrifugation, washed several timeswith ether and vacuum dried to give 1.2 g of the desired product as anoff white solid, m.p. 165°-168° C.

According to the methods outlined hereinabove in Flowsheet B anddescribed in detail in Examples 73-75, the compounds of this inventionlisted herein-below in List 8 can be prepared. These methods areapplicable to the preparation of the compounds of this invention by oneskilled in the art.

List 8

3-Methyl-2-[2-[[[-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[2-[[[-3-(tetradecyloxy)phenyl)acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[2-[[[-2-(tetradecyloxy)phenyl)acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[2-[[[3-chloro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[2-[[[3-chloro-2-(tetradecyloxy)phenyl]acetyl)amino]phenyl]thiazolium chloride

3-Methyl-2-[2-[[[3-fluoro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[2-[[[3-fluoro-2-(tetradecyloxy)phenyl]acetyl]amino)phenyl]thiazolium chloride

3-Methyl-2-[2-[[[3-acetyl-2-(tetradecyloxy)phenyl]acetyl]amino]Phenyl]thiazolium chloride

3-Methyl-2-[2-[[[3-t-butyl-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[2-[[[3-t-butyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[2-[[[3-methoxy-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[2-[[[3-methoxy-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[2-[[[2-chloro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[2-[[[4-chloro-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[2-[[[4-t-butyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[3-[[[3-chloro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[3-[[[3-chloro-2-(dodecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[3-[[[3-fluoro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[3-[[[4-(hexadecyloxy) phenyl]acetyl]amino]phenyl]thiazoliumchloride

3-Methyl-2-[3-[[[3-fluoro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[3-[[[3-fluoro-2-(dodecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[3-[[[3-acetyl-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[3-[[[3-acetyl-4-(dodecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[3-[[[3-acetyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[3-[[[3-t-butyl-4-(dodecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[3-[[[2-chloro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[3-[[[4-chloro-3-(dodecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[3-[[[4-chloro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[3-[[[4-chloro-2-(dodecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[3-[[[4-t-butyl-3-(decyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[3-[[[4-methoxy-3-(dodecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[3-[[[4-methoxy-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[3-[[[4-methoxy-2-(dodecyloxy)phenyl]acetyl]amino]5-Methylthiazolium chloride

3-Methyl-2-[4-[[[-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[4-[[[-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[4-[[[-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[4-[[[3-acetyl-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[4-[[[3-acetyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[4-[[[3-t-butyl-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[4-[[[3-t-butyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[4-[[[3-methoxy-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[4-[[[3-methoxy-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[4-[[[2-chloro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[4-[[[4-chloro-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[4-[[[4-chloro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[4-[[[4-t-butyl-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[4-[[[4-t-butyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[4-[[[4-methoxy-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-Methyl-2-[4-[[[4-methoxy-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-ethyl-2-[2-[[[-4-(tetradecyloxy) phenyl]acetyl]amino]phenyl]thiazoliumchloride

3-ethyl-2-[2-[[[-3-(tetradecyloxy) phenyl]acetyl]amino]phenyl]thiazoliumchloride

3-ethyl-2-[2-[[[-2-(tetradecyloxy) phenyl]acetyl]amino]phenyl]thiazoliumchloride

3-ethyl-2-[2-[[[3-chloro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-ethyl-2-[2-[[[3-chloro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-ethyl-2-[2-[[[3-fluoro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-ethyl-2-[2-[[[3-fluoro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-ethyl-2-[2-[[[3-acetyl-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-ethyl-2-[2-[[[3-acetyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-ethyl-2-[2-[[[3-t-butyl-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-ethyl-2-[3-[[[-2-(tetradecyloxy) phenyl]acetyl]amino]phenyl]thiazoliumchloride

3-ethyl-2-[3-[[[3-chloro-4-(octyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-ethyl-2-[3-[[[3-chloro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-ethyl-2-[3-[[[3-fluoro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-ethyl-2-[3-[[[3-fluoro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-ethyl-2-[3-[[[3-acetyl-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-ethyl-2-[3-[[[3-acetyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-ethyl-2-[3-[[[3-t-butyl-4-(decyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-ethyl-2-[3-[[[3-t-butyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-ethyl-2-[3-[[[3-methoxy-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-ethyl-2-[3-[[[2-chloro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-ethyl-2-[3-[[[4-chloro-3-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-ethyl-2-[3-[[[4-chloro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-ethyl-2-[4-[[[-2-(tetradecyloxy) phenyl]acetyl]amino]phenyl]thiazoliumchloride

3-ethyl-2-[4-[[[3-chloro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-ethyl-2-[4-[[[3-chloro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-ethyl-2-[4-[[[3-methoxy-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-ethyl-2-[4-[[[2-chloro-4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-ethyl-2-[4-[[[4-chloro-3-(dodecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-ethyl-2-[4-[[[4-chloro-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

3-ethyl-2-[4-[[[4-t-butyl-2-(tetradecyloxy)phenyl]acetyl]amino]phenyl]thiazolium chloride

EXAMPLE 76 p-Nitrophenyltetradecyl ether

A mixture of 75 g of p-nitrophenol, 149.5 g of 1-bromotetradecane, 26.96g of sodium hydroxide, 2.18 g of methyltricaprylylammonium chloride in400 ml of toluene and 400 ml of water is refluxed for 65 hours. Theorganic layer is separated, washed with 1N sodium hydroxide followed by1N hydrochloric acid. The organic layer is dried and evaporated to aresidue which is crystallized from petroleum ether to give the desiredproduct as a white solid, m.p. 57°-60° C.

EXAMPLE 77 p-(Tetradecyloxy)aniline

A mixture of 30 g of p-nitrophenyltetradecyl ether, 2 g of 10%palladium-on-carbon in 150 ml of ethyl alcohol and 20 ml of ethylacetate is shaken under pressurized hydrogen for 18 hours. The mixtureis filtered and the filtrate evaporated. The residue is crystallizedfrom hexanes to give 25.7 g of the desired product as a white solid,m.p. 65°-68° C.

EXAMPLE 78 3-(2-Bromomethyl)benzoyl chloride

To a mixture of 14.5 g of 3-(bromomethyl)benzoic acid and 11.41 g ofoxalyl chloride in 100 ml of methylene chloride is added 5 drops ofN,N-dimethylformamide followed by stirring at room temperature for 5hours. The solvent is evaporated and the residue dissolved inether:hexanes then filtered through diatomaceous earth. The filtrate isevaporated to give 15.4 g of the desired compound as a yellow liquid.

EXAMPLE 79 3-(Bromomethyl)-N-[4-(tetradecyloxy)phenyl]benzamide

To a mixture of 20.15 g of p-(tetradecyloxy)aniline and 20.87 g ofpyridine in 150 ml of tetrahydrofuran cooled to 0° C. is added asolution of 15.4 g of 3-(2-bromomethyl)benzoyl chloride in 150 ml oftetrahydrofuran over 10 minutes. The mixture is stirred for 20 minutesat 0° C. and 20 minutes at room temperature. The mixture is diluted withchloroform and washed with 1N hydrochloric acid. The organic layer isdried and evaporated to a residue which is dissolved in hot acetone and25 g of lithium bromide. The mixture is heated on a steam bath until allthe solid dissolves. The solvent is evaporated and the residuepartitioned between water and chloroform. The organic layer isseparated, dried and filtered through a pad of silica gel. The solventis removed and the residue crystallized from carbon tetrachloride:hexaneto give 18.5 g of the desired product as a white solid, m.p. 140°-142°C.

EXAMPLE 805-Methyl-3-[[3-[[[4-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazoliumbromide

A mixture of 5.5 g of3-(bromomethyl)-N-[4-(tetradecyloxy)phenyl]benzamide and 3.26 g of5-methylthiazole in 60 ml of acetonitrile is refluxed under argon for 3hours. The mixture is poured into 60 ml of acetonitrile and cooled toroom temperature. The solid is collected, washed with ether andcrystallized from acetonitrile to give 4.7 g of the desired product as awhite solid, m.p. 123°-125° C.

According to the methods outlined hereinabove in Flowsheet H anddescribed in detail in Examples 76-80, the compounds of this inventionlisted hereinbelow in List 9 can be prepared. These methods areapplicable to the preparation of the compounds of this invention by onskilled in the art.

List 9

3-[[2-[[[-4-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

3-[[2-[[[3-methoxy-4-(tetradecyloxy)phenyl]amino)carbonyl]phenyl]methyl)thiazolium bromide

3-[[2-[[[3-methoxy-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

3-[[2-[[[2-chloro-4-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

3-[[2-[[[4-chloro-3-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

3-[[2-[[[4-t-butyl-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

3-[[2-[[[4-methoxy-3-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

3-([2-[[[4-methoxy-2-(tetradecyloxy)phenyl]amino)carbonyl]phenyl]methyl]thiazolium bromide

3-[[3-[[[-4-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

3-[[3-[[[-3-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

3-[[3-[[[3-chloro-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

3-[[3-[[[3-fluoro-4-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

3-[[3-[[[3-fluoro-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

3-[[3-[[[3-methoxy-4-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

3-[[3-[[[3-methoxy-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

3-[[3-[[[2-chloro-4-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

3-[[4-[[[-3-(hexadecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

3-[[4-[[[-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

3-[[4-[[[-2-(hexadecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

3-[[4-[[[3-chloro-4-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

3-[[4-[[[3-chloro-4-(hexadecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

3-[[4-[[[3-chloro-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

3-[[4-[[[3-acetyl-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

3-[[4-[[[3-acetyl-2-(hexadecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

3-[[4-[[[3-t-butyl-4-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

3-[[4-[[[3-t-butyl-4-(hexadecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

3-[[4-[[[3-t-butyl-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

3-[[4-[[[3-methoxy-4-(hexadecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

3-[[4-[[[3-methoxy-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

3-[[4-[[[3-methoxy-2-(hexadecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

3-[[4-[[[2-chloro-4-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[-4-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[-3-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[3-chloro-4-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[3-chloro-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[3-fluoro-4-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[3-fluoro-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[3-acetyl-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[3-t-butyl-4-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[3-t-butyl-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[3-methoxy-4-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[3-methoxy-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[2-chloro-4-(tetradecyloxy)phenyl)amino)carbonyl)phenyl)methyl]thiazolium bromide

5-Methyl-3-[[2-[[[4-chloro-3-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[2-[[[4-t-butyl-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[3-chloro-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[3-chloro-2-(dodecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[3-fluoro-4-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[3-fluoro-4-(dodecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[3-fluoro-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[3-fluoro-2-(dodecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[3-acetyl-4-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[3-acetyl-4-(dodecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[3-acetyl-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[3-t-butyl-4-(dodecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[2-chloro-4-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[4-chloro-3-(dodecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[4-chloro-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[4-chloro-2-(dodecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[4-t-butyl-3-(decyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[4-methoxy-3-(hexadecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[4-methoxy-2-(tetradecyloxy)phenyl]amino]carbonyl)phenyl]methyl]thiazolium bromide

5-Methyl-3-[[3-[[[4-methoxy-2-(dodecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[-4-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[-3-(tetradecyloxy)phenyl]amino)carbonyl]phenyl]methyl)thiazolium bromide

5-Methyl-3-[[4-[[[-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[3-acetyl-4-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[3-acetyl-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[3-t-butyl-4-(decyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[3-t-butyl-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[3-methoxy-4-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[3-methoxy-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[2-chloro-4-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[4-chloro-3-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[4-chloro-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[4-t-butyl-3-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[4-t-butyl-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl)methyl]thiazolium bromide

5-Methyl-3-[[4-[[[4-methoxy-3-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

5-Methyl-3-[[4-[[[4-methoxy-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[[-4-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[[2-chloro-4-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[[4-chloro-3-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-[[[4-chloro-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[2-([[4-t-butyl-3-(tetradecyloxy)phenyl]amino]carbonyl)phenyl)methyl]thiazolium bromide

2-Methyl-3-[[2-[[[4-methoxy-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[-4-(tetradecyloxy)phenyl]amino]carbonyl)phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[-3-(tetradecyloxy)phenyl]amino)carbonyl)phenyl]methyl)thiazolium bromide

2-Methyl-3-[[3-[[[-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[3-chloro-4-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[3-chloro-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[3-fluoro-4-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[3-fluoro-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[2-chloro-4-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[3-[[[4-t-butyl-3-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[[3-fluoro-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[[3-acetyl-4-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[[3-acetyl-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl)methyl]thiazolium bromide

2-Methyl-3-[[4-[[[3-methoxy-4-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[[4-methoxy-3-(tetradecyloxy)phenyl]amino)carbonyl]phenyl]methyl]thiazolium bromide

2-Methyl-3-[[4-[[[4-methoxy-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[-4-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[-3-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl)methyl)thiazolium bromide

4-Methyl-3-[[2-[[[3-chloro-4-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[3-chloro-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[3-fluoro-4-(tetradecyloxy)phenyl]amino)carbonyl]phenyl]methyl)thiazolium bromide

4-Methyl-3-[[2-[[[3-fluoro-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl)methyl]thiazolium bromide

4-Methyl-3-[[2-[[[3-acetyl-4-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[3-acetyl-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[2-[[[3-t-butyl-4-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[3-chloro-4-(octyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[3-chloro-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[3-fluoro-4-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[3-fluoro-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[3-acetyl-4-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[3-acetyl-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[3-t-butyl-4-(decyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[3-t-butyl-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[3-methoxy-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[2-chloro-4-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[4-chloro-3-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[3-[[[4-chloro-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[3-chloro-4-(tetradecyloxy)phenyl)amino]carbonyl)phenyl]methyl)thiazolium bromide

4-Methyl-3-[[4-[[[3-chloro-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[3-methoxy-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[2-chloro-4-(tetradecyloxy)phenyl)amino]carbonyl]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[4-chloro-3-(dodecyloxy)phenyl]amino)carbonyl)phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[4-chloro-2-(tetradecyloxy)phenyl]amino]carbonyl]phenyl]methyl]thiazolium bromide

4-Methyl-3-[[4-[[[4-t-butyl-2-(tetradecyloxy)phenyl]amino]carbonyl)phenyl]methyl]thiazolium bromide

EXAMPLE 81 N-[3-(Hydroxymethyl)phenyl]-4-(tetradecyloxy)benzeneacetamide

To a solution of 15.5 g of m-aminobenzyl alcohol and 36.21 g of pyridinein 250 ml of tetrahydrofuran, cooled to 0° C. is added over 40 minutes asolution of 42 g of p-tetradecyloxyphenylacetyl chloride in 250 ml oftetrahydrofuran. The mixture is stirred overnight at room temperatureand the solvent is evaporated. The residue is partitioned between waterand chloroform with some heating to afford a complete solution. The hotchloroform solution is washed with warm water and warm dilutehydrochloric acid. The organic layer is dried and evaporated to aresidue Which is crystallized from carbon tetrachloride to give 40 g ofthe desired product as a white solid.

EXAMPLE 82 N-[3-(Bromomethyl)phenyl]-4-tetradecyloxy)benzeneacetamide

A mixture of 20 g ofN-[3-(hydroxymethyl)phenyl]-4-(tetradecyloxy)benzeneacetamide, 160 ml of30% HBr in acetic acid and 60 ml of chloroform is refluxed for 2 hours.The mixture is poured into water and extracted with chloroform. Theorganic layer is washed with water, saturated with sodium bicarbonate,dried and filtered through a short pad of silica gel. The solvent isevaporated and the residue crystallized from carbon tetrachloride:hexaneto give 18 g of the desired product as a white solid.

EXAMPLE 834-(Tetradecyloxy)-N-[3-(2-thiazolylmethyl)phenyl]benzeneacetamide

A mixture of 6 g ofN-[3-(bromomethyl)phenyl]-4-tetradecyloxy)benzeneacetamide, 3.83 g of2-(trimethylstannyl)thiazole and 407.63 mg ofdichlorobis(triphenylphosphine)palladium in 100 ml of tetrahydrofuran isrefluxed under argon for 14 hours. The mixture is filtered through a padof silica gel followed by ether washing. The organic layer is washedwith 1N sodium hydroxide, dried and evaporated to a residue which ischromatographed on silica gel eluting with 2:1 hexane:ethyl acetate togive 1.4 g of the desired product as an off-white powder.

EXAMPLE 844-(Tetradecyloxy)-N-[3-(2-thiazolylmethyl)phenyl]benzeneacetamidemonohydrochloride

To a tetrahydrofuran:ether solution of4-(tetradecyloxy)-N-[3-(2-thiazolylmethyl)phenyl]benzeneacetamide isadded ether saturated with hydrogen chloride. The resulting solid iscollected by centrifugation and dried in vacuum to give 0.18 g of thedesired product as a tan solid, m.p. 155°-158° C.

EXAMPLE 853-Methyl-2-[[3-[[[4-(tetradecyloxy)phenyl]acetyl]amino]phenyl]methyl]thiazoliumbromide

A mixture of 500 mg of4-(tetradecyloxy)-N-[3-(2-thiazolylmethyl)phenyl]benzeneacetamide and6.13 g of methyl iodide in 12 ml of acetonitrile is heated in a pressurevessel under argon for 2 hours. The solvent is removed and the residuedissolved in a minimum of chloroform followed by dilution with ether.The resulting solid is collected by centrifugation, washed with etherand vacuum dried to give 0.6 g of the desired compound as a tan solid,m.p. 192°-195° C.

EXAMPLE 86 N-[4-(Hydroxymethyl)phenyl]-4-(tetradecyloxy)benzamide

To a mixture of 9.75 g of p-aminobenzyl alcohol and 19.27 g of pyridinein 230 ml of methylene chloride cooled to 0° C. is added over 35 minutesa solution of 21.5 g of 4-tetradecyloxybenzoyl chloride in 230 ml ofmethylene chloride. The mixture is stirred at room temperature for 2hours and diluted with chloroform. The mixture is heated to dissolveinsolubles, washed with hot water and hot dilute hydrochloric acid thendried. The mixture is filtered hot and the solvent evaporated to aresidue which is crystallized from tetrahydrofuran:hexane to give 18.1 gof the desired product as a yellow powder, m.p. 140°-145° C.

EXAMPLE 87 4-[[[(4-(Tetradecyloxy)phenyl]methyl]amino]benzenemethanol

To a suspension of 13 g ofN-[4-(hydroxymethyl)phenyl]-4-(tetradecyloxy)benzamide in 250 ml oftetrahydrofuran is added dropwise with stirring under argon 59.14 ml of1 molar lithium aluminum hydride in tetrahydrofuran. The mixture isstirred at room temperature for 0.5 hours and refluxed for 5 hours.Ethyl acetate is added dropwise followed by water. The mixture isfiltered and the cake washed with ether. The filtrate is evaporated to aresidue which is purified by chromatography on silica gel with 2:1chloroform:hexane to give the desired product.

EXAMPLE 88 4-[[[4-(Tetradecyloxy)phenyl]methyl]amino]benzenemethanol

A mixture of 20 g of 7.73 g of p-aminobenzyl alcohol and 3.95 g ofsodium cyanoborohydride in 200 ml of ethyl alcohol is refluxed for 7hours. The mixture is poured into water and extracted with warmchloroform. The organic layer is washed with saturated sodiumbicarbonate, dried and evaporated to a residue which is crystallizedfrom methyl alcohol followed by purification on silica gel using 3:1hexane:ethyl acetate to give 9.0 g of the desired product as a yellowsolid, m.p. 85°-87° C.

EXAMPLE 89N-[4-(Hydroxymethyl)phenyl]-N-[[4-tetradecyloxy)phenyl]methyl]acetamide

To a 0° C. solution of 8.3 g of4-[[[4-(tetradecyloxy)phenyl]methyl]amino]benzenemethanol in 70 ml ofmethylene chloride containing 6.17 g of pyridine is added 5.36 g ofacetyl chloride in 10 ml of methylene chloride followed by stirring atroom temperature for 1.5 hours. The mixture is poured into water andextracted with chloroform. The organic layer is separated and washedwith dilute hydrochloric acid and saturated sodium bicarbonate. Theorganic layer is dried and evaporated to a residue which is dissolved in80 ml of ethyl alcohol, 1.3 ml of water and 1.09 g of sodium hydroxide.The mixture is stirred for 40 minutes, poured into water and extractedwith ether. The organic layer is dried and evaporated to a residue whichis crystallized from carbon tetrachloride:petroleum ether to give 7.1 gof the desired product as a white solid, m.p. 76°-79° C.

EXAMPLE 90N-[4-(Bromomethyl)phenyl]-N-[[4-(tetradecyloxy)phenyl]methyl]acetamide

To a solution of 6.9 g ofN-[4-(hydroxymethyl)phenyl]-N-[[4-tetradecyloxy)phenyl]methyl]acetamidein 100 ml of tetrahydrofuran is added 2.25 g of methanesulfonyl chlorideand 1.79 g of triethylamine followed by stirring for 3.5 hours. Alsoadded is 12.81 g of lithium bromide followed by stirring for 18 hours.The mixture is poured into water and extracted with ether. The organiclayer is dried and evaporated to a residue which is crystallized frompetroleum ether to give 6.8 g of the desired product as a white solid,m.p. 46°-49° C.

EXAMPLE 913-[[4-acetyl[[4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methylthiazolium bromide

A mixture of 3.5 g of N-[4-(bromomethyl)phenyl]-N-[[4-(tetradecyloxy)phenyl]methyl]acetamide and 1.96 g of5-methylthiazole in 50 ml of acetonitrile is refluxed under argon for4.5 hours. The solvent is evaporated and the residue mixed with ether.The solid is collected by centrifugation, washed with ether severaltimes and dried under vacuum to give 2.8 g of the desired product as awhite powder, m.p. 95°-98° C.

According to the methods outlined hereinabove in Flowsheet C anddescribed in detail in Examples 29-32, 64, 65, 86-91, the compounds ofthis invention listed hereinbelow in List 10 can be prepared. Thesemethods are applicable to the preparation of the compounds of thisinvention by on skilled in the art.

List 10

3-[[4-[Acetyl[[4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[Acetyl[[4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[4-[Acetyl[[4-(dodecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[Acetyl[[4-(hexadecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[4-[Acetyl[[3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[Acetyl[[3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[4-[Acetyl[[3-(dodecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[Acetyl[[3-(dodecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[4-[Acetyl[[3-chloro-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[Acetyl[[3-chloro-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[4-[Acetyl[[3-fluoro-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[Acetyl[[3-fluoro-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[4-[Acetyl[[3-t-butyl-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[Acetyl[[3-t-butyl-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[4-[Acetyl[[3-methoxy-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[Acetyl[[3-methoxy-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[4-[Acetyl[[4-chloro-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[Acetyl[[4-chloro-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[4-[Acetyl[[4-t-butyl-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[Acetyl[[4-t-butyl-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[4-[Acetyl[[4-methoxy-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[Acetyl[[4-methoxy-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[4-[[1-oxopropyl][[4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[[1-oxopropyl][[4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[4-[[1-oxopropyl][[4-(dodecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[[1-oxopropyl][[4-(dodecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[4-[[1-oxopropyl][[3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[[1-oxopropyl][[3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[4-[[1-oxopropyl][[3-(dodecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[[1-oxopropyl][[3-(dodecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[4-[[1-oxopropyl][[3-chloro-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[[1-oxopropyl][[3-chloro-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[4-[[1-oxopropyl][[3-fluoro-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[[1-oxopropyl][[3-fluoro-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[4-[[1-oxopropyl][[3-t-butyl-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[[1-oxopropyl][[3-t-butyl-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[4-[[1-oxopropyl][[3-methoxy-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[[1-oxopropyl][[3-methoxy-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[4-[[1-oxopropyl][[4-chloro-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[[1-oxopropyl][[4-chloro-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[4-[[1-oxopropyl][[4-t-butyl-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[[1-oxopropyl][[4-t-butyl-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[4-[[1-oxopropyl][[4-methoxy-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[4-[[1-oxopropyl][[4-methoxy-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[3-[Acetyl[[4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[3-[Acetyl[[4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[3-[Acetyl[[4-(hexadecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[3-[Acetyl[[4-(dodecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[3-[Acetyl[[3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[3-[Acetyl[[3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[3-[Acetyl[[3-(hexadecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[3-[Acetyl[[3-(hexadecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[3-[Acetyl[[3-chloro-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[3-[Acetyl[[3-chloro-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[3-[Acetyl[[3-chloro-4-(hexadecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[3-[Acetyl[[3-chloro-4-(hexadecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[3-[Acetyl[[3-fluoro-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[3-[Acetyl[[3-fluoro-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[3-[Acetyl[[3-t-butyl-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[3-[Acetyl[[3-t-butyl-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[3-[Acetyl[[3-methoxy-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[3-[Acetyl[[3-methoxy-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[3-[Acetyl[[4-chloro-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[3-[Acetyl[[4-chloro-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[3-[Acetyl[[4-t-butyl-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[3-[Acetyl[[4-t-butyl-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[3-[Acetyl[[4-methoxy-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[3-[Acetyl[[4-methoxy-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[3-[[1-oxopropyl][[4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[3-[[1-oxopropyl][[4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[3-[[1-oxopropyl][[3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[3-[[1-oxopropyl][[3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[3-[[1-oxopropyl][[3-chloro-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[3-[[1-oxopropyl][[3-chloro-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[3-[[1-oxopropyl][[3-fluoro-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[3-[[1-oxopropyl][[3-fluoro-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[3-[[1-oxopropyl][[3-t-butyl-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[3-[[1-oxopropyl][[3-t-butyl-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[3-[[1-oxopropyl][[3-methoxy-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[3-[[1-oxopropyl][[3-methoxy-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[3-[[1-oxopropyl][[4-chloro-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[3-[[1-oxopropyl][[4-chloro-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[3-[[1-oxopropyl][[4-t-butyl-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[3-[[1-oxopropyl][[4-t-butyl-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[3-[[-oxopropyl][[4-methoxy-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]thiazoliumbromide

3-[[3-[[1-oxopropyl][[4-methoxy-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[2-[Acetyl[[4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[2-[Acetyl[[3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[2-[Acetyl[[3-chloro-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[2-[Acetyl[[3-fluoro-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[2-[Acetyl[[3-methoxy-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[2-[Acetyl[[4-chloro-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[2-[Acetyl[[4-methoxy-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-5-methyl-thiazoliumbromide

3-[[4-[Acetyl[[4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]pyridiniumbromide

3-[[4-[Acetyl[[4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,4-dimethyl-pyridiniumbromide

3-[[4-[Acetyl[[4-(dodecyloxy)phenyl]methyl]amino]phenyl]methyl]pyridiniumbromide

3-[[4-[Acetyl[[4-(hexadecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,4-dimethyl-pyridiniumbromide

3-[[4-[Acetyl[[3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]pyridiniumbromide

3-[[4-[Acetyl[[3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,4-dimethyl-pyridiniumbromide

3-[[4-[Acetyl[[3-(dodecyloxy)phenyl]methyl]amino]phenyl]methyl]pyridiniumbromide

3-[[4-[Acetyl[[3-(dodecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,4-dimethyl-pyridiniumbromide

3-[[4-[Acetyl[[3-chloro-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]pyridiniumbromide

3-[[4-[Acetyl[[3-chloro-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,4-dimethyl-pyridiniumbromide

3-[[4-[Acetyl[[3-fluoro-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]pyridiniumbromide

3-[[4-[Acetyl[[3-fluoro-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,4-dimethyl-pyridiniumbromide

3-[[4-[Acetyl[[3-t-butyl-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]pyridiniumbromide

3-[[4-[Acetyl[[3-t-butyl-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,4-dimethyl-pyridiniumbromide

3-[[4-[Acetyl[[3-methoxy-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]pyridiniumbromide

3-[[4-[Acetyl[[3-methoxy-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,4-dimethyl-pyridiniumbromide

3-[[4-[Acetyl[[4-chloro-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]pyridiniumbromide

3-[[4-[Acetyl[[4-chloro-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,4-dimethyl-pyridiniumbromide

3-[[4-[Acetyl[[4-t-butyl-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]pyridiniumbromide

3-[[4-[Acetyl[[4-t-butyl-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,4-dimethyl-pyridiniumbromide

3-[[4-[Acetyl[[4-methoxy-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]pyridiniumbromide

3-[[4-[Acetyl[[4-methoxy-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,4-dimethyl-pyridiniumbromide

3-[[3-[Acetyl[[4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,4-dimethyl-pyridiniumbromide

3-[[3-[Acetyl[[4-(hexadecyloxy)phenyl]methyl]amino]phenyl]methyl]pyridiniumbromide

3-[[3-[Acetyl[[4-(dodecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,4-dimethyl-pyridiniumbromide

3-[[3-[Acetyl[[3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]pyridiniumbromide

3-[[3-[Acetyl[[3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,4-dimethyl-pyridiniumbromide

3-[[3-[Acetyl[[3-(hexadecyloxy)phenyl]methyl]amino]phenyl]methyl]pyridiniumbromide

3-[[3-[Acetyl[[3-(hexadecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,4-dimethyl-pyridiniumbromide

3-[[3-[Acetyl[[3-chloro-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]pyridiniumbromide

3-[[3-[Acetyl[[3-chloro-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,4-dimethyl-pyridiniumbromide

3-[[3-[Acetyl[[3-chloro-4-(hexadecyloxy)phenyl]methyl]amino]phenyl]methyl]pyridiniumbromide

3-[[3-[Acetyl[[3-chloro-4-(hexadecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,4-dimethyl-pyridiniumbromide

3-[[3-[Acetyl[[3-fluoro-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]pyridiniumbromide

3-[[3-[Acetyl[[3-fluoro-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,4-dimethyl-pyridiniumbromide

3-[[3-[Acetyl[[3-t-butyl-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]pyridiniumbromide

3-[[3-[Acetyl[[3-t-butyl-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,4-dimethyl-pyridiniumbromide

3-[[3-[Acetyl[[3-methoxy-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]pyridiniumbromide

3-[[3-[Acetyl[[3-methoxy-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,4-dimethyl-pyridiniumbromide

3-[[3-[Acetyl[[4-chloro-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]pyridiniumbromide

3-[[3-[Acetyl[[4-chloro-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,4-dimethyl-pyridiniumbromide

3-[[3-[Acetyl[[4-t-butyl-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]pyridiniumbromide

3-[[3-[Acetyl[[4-t-butyl-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,4-dimethyl-pyridiniumbromide

3-[[3-[Acetyl[[4-methoxy-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]pyridiniumbromide

3-[[3-[Acetyl[[4-methoxy-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,4-dimethyl-pyridiniumbromide

3-[[3-[[1-oxopropyl][[4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]pyridiniumbromide

3-[[3-[[1-oxopropyl][[4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,4-dimethyl-pyridiniumbromide

3-[[3-[[1-oxopropyl][[3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]pyridiniumbromide

3-[[3-[[1-oxopropyl][[3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,4-dimethyl-pyridiniumbromide

3-[[2-[Acetyl[[4-(tetradecyloxy)phenyl]methyl]amino]Phenyl]methyl]-3,4-dimethyl-pyridiniumbromide

3-[[2-[Acetyl[[3-(tetradecyloxy)Phenyl)methyl)amino]Phenyl)methyl]-3,4-dimethyl-pyridinium bromide

3-[[2-[Acetyl[[3-chloro-4-(tetradecyloxy)Phenyl)methyl]amino]phenyl]methyl]-3,4-dimethyl-pyridinium bromide

3-[[2-[Acetyl[[3-fluoro-4-(tetradecyloxy)Phenyl)methyl]amino]Phenyl]methyl]-3,4-dimethyl-pyridinium bromide

3-[[2-[Acetyl[[3-methoxy-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,4-dimethyl-pyridiniumbromide

3-[[2-[Acetyl[[4-chloro-3-(tetradecyloxy)Phenyl]methyl]amino]Phenyl]methyl]-3,4-dimethyl-pyridiniumbromide

3-[[2-[Acetyl[[4-methoxy-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,4-dimethyl-pyridiniumbromide

3-[[4-[Acetyl[[4-(tetradecyloxy)Phenyl]methyl]amino]Phenyl]methyl]imidaxo[1,5-a]Pyridiniumbromide

3-[[4-[Acetyl[[4-(tetradecyloxy)phenyl]methyl]amino]Phenyl]methyl]-3,5-dimethyl-pyridiniumbromide

3-[[4-[Acetyl[[4-(dodecyloxy)Phenyl]methyl]amino]phenyl]methyl]imidaxo[1,5-a]pyridiniumbromide

3-[[4-[Acetyl[[4-(hexadecyloxy)phenyl]methyl]amino]Phenyl)methyl]-3,5-dimethyl-pyridiniumbromide

3-[[4-[Acetyl[[3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]imidaxo[1,5-a]pyridiniumbromide

3-[[4-[Acetyl[[3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,5-dimethyl-pyridiniumbromide

3-[[4-[Acetyl[[3-(dodecyloxy)phenyl]methyl]amino]phenyl]methyl]imidaxo[1,5-a]pyridiniumbromide

3-[[4-[Acetyl[[3-(dodecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,5-dimethyl-pyridiniumbromide

3-[[4-[Acetyl[[3-chloro-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]imidaxo[1,5-a]pyridiniumbromide

3-[[4-[Acetyl[[3-chloro-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,5-dimethyl-pyridiniumbromide

3-[[4-[Acetyl[[3-fluoro-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]imidaxo[1,5-a]pyridiniumbromide

3-[[4-[Acetyl[[3-fluoro-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,5-dimethyl-pyridiniumbromide

3-[[4-[Acetyl[[3-t-butyl-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]imidaxo[1,5-a]pyridiniumbromide

3-[[4-[Acetyl[[3-t-butyl-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,5-dimethyl-pyridiniumbromide

3-[[4-[Acetyl[[3-methoxy-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]imidaxo[1,5-a]pyridiniumbromide

3-[[4-[Acetyl[[3-methoxy-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,5-dimethyl-pyridiniumbromide

3-[[4-[Acetyl[[4-chloro-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]imidaxo[1,5-a]pyridiniumbromide

3-[[4-[Acetyl[[4-chloro-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,5-dimethyl-pyridiniumbromide

3-[[4-[Acetyl[[4-t-butyl-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]imidaxo[1,5-a]pyridiniumbromide

3-[[4-[Acetyl[[4-t-butyl-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,5-dimethyl-pyridiniumbromide

3-[[4-[Acetyl[[4-methoxy-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]imidaxo[1,5-a]pyridiniumbromide

3-[[4-[Acetyl[[4-methoxy-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,5-dimethyl-pyridiniumbromide

3-[[3-[Acetyl[[4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,5-dimethyl-pyridiniumbromide

3-[[3-[Acetyl[[4-(hexadecyloxy)phenyl]methyl]amino]phenyl]methyl]imidaxo[1,5-a]pyridiniumbromide

3-[[3-[Acetyl[[4-(dodecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,5-dimethyl-pyridiniumbromide

3-[[3-[Acetyl[[3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]imidaxo[1,5-a]pyridiniumbromide

3-[[3-[Acetyl[[3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,5-dimethyl-pyridiniumbromide

3-[[3-[Acetyl[[3-(hexadecyloxy)phenyl]methyl]amino]phenyl]methyl]imidaxo[1,5-a]pyridiniumbromide

3-[[3-[Acetyl[[3-(hexadecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,5-dimethyl-pyridiniumbromide

3-[[3-[Acetyl[[3-chloro-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]imidaxo[1,5-a]pyridiniumbromide

3-[[3-[Acetyl[[3-chloro-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,5-dimethyl-pyridiniumbromide

3-[[3-[Acetyl[[3-chloro-4-(hexadecyloxy)phenyl]methyl]amino]phenyl]methyl]imidaxo[1,5-a]pyridiniumbromide

3-[[3-[Acetyl[[3-chloro-4-(hexadecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,5-dimethyl-pyridiniumbromide

3-[[3-[Acetyl[[3-fluoro-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]imidaxo[1,5-a]pyridiniumbromide

3-[[3-[Acetyl[[3-fluoro-4-(tetradecyloxy)Phenyl]methyl]amino]Phenyl]methyl]-3,5-dimethyl-pyridiniumbromide

3-[[3-[Acetyl[[3-t-butyl-4-(tetradecyloxy)Phenyl]methyl]amino]Phenyl]methyl]imidaxo[1,5-a]pyridiniumbromide

3-[[3-[Acetyl[[3-t-butyl-4-(tetradecyloxy)Phenyl)methyl]amino]Phenyl]methyl]-3,5-dimethyl-pyridinium bromide

3-[[3-[Acetyl[[3-methoxy-4-(tetradecyloxy)phenyl]methyl]amino]Phenyl]methyl]imidaxo[1,5-a]Pyridiniumbromide

3-[[3-[Acetyl[[3-methoxy-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,5-dimethyl-pyridiniumbromide

3-[[3-[Acetyl[[4-chloro-3-(tetradecyloxy)Phenyl]methyl]amino]phenyl]methyl]imidaxo[1,5-a]pyridiniumbromide

3-[[3-[Acetyl[[4-chloro-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,5-dimethyl-pyridiniumbromide

3-[[3-[Acetyl[[4-t-butyl-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]imidaxo[1,5-a]pyridiniumbromide

3-[[3-[Acetyl[[4-t-butyl-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,5-dimethyl-pyridiniumbromide

3-[[3-[Acetyl[[4-methoxy-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]imidaxo[1,5-a]pyridiniumbromide

3-[[3-[Acetyl[[4-methoxy-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,5-dimethyl-pyridiniumbromide

3-[[3-[[1-oxopropyl][[4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]imidaxo[1,5-a]pyridiniumbromide

3-[[3-[[1-oxopropyl][[4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,5-dimethyl-pyridiniumbromide

3-[[3-[[1-oxopropyl][[3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]imidaxo[1,5-a]pyridiniumbromide

3-[[3-[[1-oxopropyl][[3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,5-dimethyl-pyridiniumbromide

3-[[2-[Acetyl[[4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,5-dimethyl-pyridiniumbromide

3-[[2-[Acetyl[[3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,5-dimethyl-pyridiniumbromide

3-[[2-[Acetyl[[3-chloro-4-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,5-dimethyl-pyridiniumbromide

3-[[2-[Acetyl[[3-fluoro-4-(tetradecyloxy)Phenyl]methyl]amino]phenyl]methyl]-3,5-dimethyl-pyridiniumbromide

3-[[2-[Acetyl[[3-methoxy-4-(tetradecyloxy)Phenyl]methyl]amino]Phenyl]methyl]-3,5-dimethyl-pyridiniumbromide

3-[[2-[Acetyl[[4-chloro-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,5-dimethyl-pyridiniumbromide

3-[[2-[Acetyl[[4-methoxy-3-(tetradecyloxy)phenyl]methyl]amino]phenyl]methyl]-3,5-dimethyl-pyridiniumbromide

We claim:
 1. A process for producing compounds of the formula: ##STR17##wherein: (A) X is a divalent radical ##STR18## wherein p is the integer0 or 1; n is the integer 0, 1 or 2; (B) R₁ represents one or moresubstituents of the aromatic ring which may be the same or different andis selected from the group consisting of:(i) C₁ -C₂₅ alkyl, C₂ -C₂₅alkenyl, C₁ -C₂₅ alkoxy, C₁ -C₂₅ thioalkyl, C₂ -C₂₅ alkenyloxy, phenyl,phenoxy, substituted phenyl and substituted phenoxy wherein thesubstituents are selected from the group consisting of C₁ -C₂₀ alkyl, C₁-C₂₀ alkoxy, halogen and trifluoromethyl; (ii) hydrogen, halogen,trifluoromethyl, cyano and nitro; (iii) --CO₂ R₄, --CONHR₃, --CHO,OCONHR₄, and --NHCOR₄ wherein R₄ is selected from the group consistingof C₁ -C₂₅ alkyl, C₂ -C₂₅ alkenyl, phenyl and substituted phenyl whereinthe substituents are selected from the group consisting of C₁ -C₂₀alkyl, C₁ -C₂₀ alkoxy, halogen and trifluoromethyl; (C) the moiety R₂represents one or more substituents of the aromatic ring which may be inany position and are selected from the group consisting of hydrogen C₁-C₅ alkyl, C₁ -C₅ alkoxy and halogen; (D) the moiety Y represents amoiety of the formula: ##STR19## wherein the moiety R₅ is one or moresubstituents of the heterocyclic ring which may be the same or differentand are selected from the groups consisting of hydrogen, C₁ -C₆ alkyl,C₁ -C₆ acyl or C₁ -C₆ alkoxy, R₆ is C₁ -C₄ alkyl; and (E) J⊖ is apharmacologically acceptable salt forming anion, which comprisestreating an acid chloride of the formula: ##STR20## with an amine of theformula: ##STR21## wherein R₈ is selected from the group consisting of--CH₂ OH and --CO₂ R₇ wherein R₇ is C₁ -C₄ alkyl, in an inert solvent togive a compound of the formula: ##STR22## when R₈ is a C₁ -C₄carboalkoxy group, treating said compound with a reducing agent to givea product of the formula: ##STR23## which is treated with eithermethanesulfonyl chloride and lithium bromide in an inert solvent orhydrogen bromide in acetic acid to give a product of the formula:##STR24## which is further alkylated with a nitrogen containingheterocycle Y' selected from: ##STR25## wherein R₅ and R₆ are as definedhereinabove in an inert solvent to give compounds of the formula:##STR26## as internal salts.